JP2018507740A - How to provide skin care using phototherapy - Google Patents

Abstract

The present invention relates in particular to a cosmetic method for providing skin care, which comprises irradiating the skin of a subject with one or more light rays, both of which provide the skin with light having a discontinuous spectrum. The invention also relates to methods for treating skin related diseases and to light emitting devices for use in these methods.

Description

  The present invention is in the field of cosmetic skin care and skin medical treatment. In particular, the present invention relates to a light emitting device for irradiating a subject's skin with phototherapy, and a cosmetic and medical treatment for improving the condition of the subject's skin or treating a skin disease with phototherapy. Methods and methods for improving skin treatment. The invention further relates to a composition for use in such a method.

  Sunlight was already used by ancient cultures to treat skin diseases. This early form of phototherapy using the sun as a light source has been shown to be effective in the treatment of acne vulgaris, a skin disease characterized by painful skin tuberculosis skin lesions. It was rediscovered in the early 19th century. As a result, phototherapy, i.e., phototherapy with the application and modification of natural light sources, is currently used as a treatment to treat a wide range of vast health conditions and clinical syndromes.

  Following the availability of lasers that emit monochromatic coherent light, it was discovered in the 1960s that low power lasers can induce hair growth in mice. This is believed to be due to the induction of intracellular signaling cascades and the resulting cellular photoresponse in skin cells.

  Human skin is divided into two layers, the epidermis and the dermis. The epidermis is a stratified squamous epithelium and acts as a barrier against foreign substances such as infectious agents. The epidermis further regulates the amount of water released from the body into the atmosphere by transdermal water loss. The epidermis consists of proliferative basal keratinocytes and differentiated keratinocytes on the basal layer. The dermis is the layer of skin between the epidermis (the dermis forms the skin with the epidermis) and the subcutaneous tissue, consists of connective tissue, and protects the body from irritation and impact. The dermis consists of three main types of cells: fibroblasts, macrophages and adipocytes.

  The keratinocytes in the basal layer, the deepest layer of the epidermis, proliferate by mitosis, daughter cells rise up the layer (epidermis layer), change shape and composition while undergoing multi-stage cell differentiation, Eventually it will be nuclear free. During that process, keratinocytes secrete keratin proteins and lipids that contribute to the formation of extracellular matrix and provide mechanical strength to the skin. Fibroblasts are cell types that synthesize extracellular matrix such as collagen. Both fibroblasts and keratinocytes play a major role in wound healing and maintaining skin integrity, elasticity and appearance (see FIG. 1), producing collagen and elastin. These molecules are known to have beneficial effects on wound healing and on improving skin elasticity and appearance. Photo-aged skin (eg, prematurely-aged skin resulting from chronic exposure to solar radiation) has a reduced collagen content and contains damaged collagen. In addition, photoaged skin has a reduced fibrotic cell content or a reduced proliferative fibroblast content and therefore exhibits reduced contractile strength and mechanical strength. Such characteristics are common for aging skin types and affect the ability of aging skin to regenerate after trauma, as well as the condition and appearance of aging skin.

  There is a need for further means and methods for improving the condition and appearance of aging skin and for means and methods for treating the skin of a subject suffering from a skin disease. The object of the present invention is to provide means and methods for cosmetic and therapeutic skin care based on phototherapy.

  It has now surprisingly been found that light of a narrow range of specific wavelength combinations has an excellent effect on the skin and can be used beneficially in phototherapy. Specifically, irradiation of skin cells with light having a discontinuous spectrum with peaks at wavelengths corresponding to green light, red light, and near infrared light causes skin cell proliferation and migration, such as occurs in wound healing. It has been found to be very beneficial for the activation process and for the production of extracellular matrix such as collagen, in particular type III collagen. Surprisingly, it has also been found that certain irradiation regimes lead to increased production of collagen.

  Accordingly, the present invention, in a first aspect, provides a cosmetic (eg, aesthetic) method for providing skin care, the method comprising irradiating the subject's skin with one or more light beams, the light beams described above. Both provide the skin with light having a discontinuous spectrum with peaks at wavelengths corresponding to green light, red light and near infrared, and the skin is illuminated by the wavelength peaks simultaneously or sequentially. The

  In a preferred embodiment of the cosmetic method according to the invention, the method further comprises the application of skin care active ingredients, preferably topical application, preferably before, during or after the step of irradiating the skin, Skincare active ingredients include carotenoids, flavonoids and polyphenols antioxidants; estrogens; vitamins and their derivatives; palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate-methionine-glutamine-arginine-arginine and Peptides containing tripeptide copper glycine-histidine-lysine; hydroxy acids; sugar amines; ceramides; metals; minerals; monoethanolamines; diethanolamines; sodium laureth sulfate; retinoids such as trans-retinoic acid; Arlonic acid; Triethanolamine; Resveratrol; Plant or algal extract containing plant molecules such as polysaccharides; Hydroquinone; Mequinol; Kojic acid; Arbutin; Mulberry; Blueberry; Cranberry; Glycyrrhiza glabra; Glycyrrhizate; Grabrazine; Pycnogenol; Pinus pinaster; Phyllanthus emblica; Ascophyllum nodosum; Aspergillus fermented material; Ferula foetida; Mitracarpus scaber (Mitracarpus scaber) Nasturtium officinale; Darus (Palmaria palmata); Nagamegishigishi (Rumex crispus); Tanjin (Salvia miltiorrhiza); Saxifraga sarmentosa; Clara (Sophora angustifolia); Entriaol; ferulic acid; phloretin; Epilobium angustifolium; niacimide; niacimide; glucosamine; resorcinol; peptide (nanopeptide 1, oligopeptide 68, oligopeptide 34, oligopeptide 51); azelaic acid; lactic acid; phytic acid; Selected from enzymes such as papain, bromelain; dipalmitoylhydroxyproline (DPHP); and humectants;

  In another preferred embodiment of the cosmetic method according to the invention, the fluence or power (irradiation dose) brought to the skin by the irradiation is preferably determined by skin cells, in keratinocyte culture or fibroblast culture. Sufficient to induce the production of collagen and / or elastin and / or to induce activation, proliferation and / or cell migration of keratinocytes, fibroblasts, primordial myofibroblasts and / or myofibroblasts It is.

  In another preferred embodiment, the one or more light beams are provided by one or more LED light sources.

  In yet another preferred embodiment, the cosmetic method according to the present invention comprises skin rejuvenation, skin moisturization and / or tension, surface and deep skin repair, skin tightening and wrinkling, eye contour improvement, skin contouring. Resulting in and / or resulting in increased brightness, wrinkles, fine lines, senile plaques, scars, stretch marks, cellulite, yellowed skin, swollen eyes, dark circles, chronic or photodamaged skin, dry skin, pigment It leads to the prevention, reduction and / or treatment of over-deposited skin, flaccid skin, skin redness, leather-like skin, photoelastic fibrosis and alopecia.

  In yet another aspect, the present invention provides a method of treating a skin-related disease by phototherapy, comprising irradiating the subject's skin with one or more light beams, both of which are applied to the skin. In contrast, light having a discontinuous spectrum with peaks at wavelengths corresponding to green light, red light and near infrared light is provided, and the skin is illuminated by the wavelength peaks simultaneously or sequentially.

  In a preferred embodiment of the treatment method according to the invention, the method further comprises the application of a topical pharmaceutical ingredient, preferably topical application, preferably before, during or after the step of irradiating the skin, Topical pharmaceutical ingredients include carotenoids, flavonoids and polyphenols antioxidants; estrogens; vitamins and their derivatives; palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate-methionine-glutamine-arginine-arginine and Peptides containing tripeptide copper glycine-histidine-lysine; hydroxy acids; sugar amines; ceramides; metals; minerals; monoethanolamines; diethanolamines; sodium laureth sulfate; retinoids such as trans-retinoic acid; Triethanolamine; resveratrol; plant or algae extract containing plant molecules such as polysaccharides; hydroquinone; mequinol; kojic acid; salicylic acid; arbutin; vitamin A derivatives such as adapalene, tazarotene; tetrinoin; Selected from: tretinoin; dipalmitoylhydroxyproline (DPHP); and a humectant.

  In another preferred embodiment of the treatment method according to the invention, the fluence or output (irradiation dose) brought about by the irradiation on the skin by phototherapy is preferably in keratinocyte culture or fibroblast culture. Or preferably also inducing skin and / or elastin production by skin cells and / or keratinocytes, fibroblasts, primordial muscle when compared to standard skin in skin taken ex vivo Sufficient to induce fibroblast and / or myofibroblast activation, proliferation and / or cell migration.

  In another preferred embodiment of the treatment method according to the invention, said one or more light beams are provided by one or more LED light sources.

  In still another preferred embodiment of the treatment method according to the present invention, the skin-related disease is acute skin wound, chronic skin wound such as skin ulcer, pressure ulcer, diabetic skin ulcer, hypertrophic scar, scar keloid, telangiectasia (Spider veins), skin atrophy, precancerous skin lesions, herpes, inflammatory acne, acne vulgaris, comedogenic or polymorphic acne, nodular cystic acne, confluent acne Acne, senile acne, and secondary acne (such as sunlight, medicinal or occupational acne), ichthyosis, ichthyosis-like condition, Darier's disease, palmokeratosis, leukoplakia and leukoplakia-like condition or Lichen and lichen planus, psoriasis of the skin, mucous membranes or nails, psoriatic rheumatism, skin atopy including eczema, dry skin, skin irritation, redness, sun erythema, actinic keratosis, skin allergy and allergic or Irritant contact dermatitis, atopic dermatitis, rosacea, pigmentation Excessive, benign pigmented lesions (lentigo, freckles, brown spots, melasma), is selected from the group formed by aged skin and lupus erythematosus.

  In yet another aspect, the present invention provides a skin care active ingredient, preferably DPHP, for use in a method of activating skin processes including collagen induction and wound healing, wherein the skin care active ingredient described above, preferably DPHP is administered topically before, during and / or after phototherapy, which involves irradiating the subject's skin with one or more rays, both of which are green, red, This results in light having a discontinuous spectrum with peaks at wavelengths corresponding to light and near infrared, and the skin is illuminated by the wavelength peaks simultaneously or sequentially.

  In yet another aspect, the present invention provides a light emitting device for irradiating a subject's skin by phototherapy, wherein the device is discontinuous with peaks at wavelengths corresponding to green light, red light and near infrared. One or more light sources configured to emit light having a spectrum, wherein the one or more light sources are configured to simultaneously or sequentially apply the wavelength peaks in the light to illuminate the surface of the skin. It is configured to leave.

  In a preferred embodiment of the light emitting device according to the invention, the peak at the distinct wavelength is emitted from a separate light source and / or the light source is collagen and / or in the skin when compared to standard skin. Or to induce the production of elastin and / or to induce activation, proliferation and / or cell migration of keratinocytes, fibroblasts, primordial myofibroblasts and / or myofibroblasts in said skin It is configured to irradiate the surface of the skin with sufficient fluence or output (irradiation dose).

  In another preferred embodiment of the light emitting device according to the present invention, the one or more light sources are provided in the form of LEDs.

  In a preferred embodiment of the light emitting device according to the present invention, the device further comprises a dispenser adapted for topical application of an active skin care ingredient or pharmaceutical ingredient before, during or after irradiation of the skin by said device, preferably The above skin care active ingredients are: antioxidants including carotenoids, flavonoids and polyphenols; estrogens; vitamins and their derivatives; palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate-methionine-glutamine-arginine Peptides containing arginine and tripeptide copper glycine-histidine-lysine; hydroxy acids; sugar amines; ceramides; metals; minerals; monoethanolamine; Hyaluronic acid; Triethanolamine; Resveratrol; Plant or algal extract containing plant molecules such as polysaccharides; Hydroquinone; Mequinol; Kojic acid; Arbutin; Mulberry; Blueberry; Cranberry; Licorice; Glycyrrhizate; Pycnogenol; Pinea Spina Star; Yukan; Ascofilm Nodomus; Aspergillus Fermented; Ferla Fetida; Mittra Carpus Skever; Ferulic acid; phloretin; willow lantern; niacimide; glucosamine; resorcinol; peptide (nanopeptide 1, oligopeptide 68, oligopeptide 34, oligope Plastid 51); azelaic acid; lactic, phytic acid; salicylic, trichloroacetic acid; enzymes, for example, papain, bromelain, dipalmitoyl hydroxyproline (DPHP); and is selected from humectants.

  The present invention provides a light emitting device for irradiating a subject's skin by phototherapy, wherein the device has a discontinuous spectrum with peaks at wavelengths in the range of 510-536 nm, 650-670 nm, and 768-792 nm. One or more light sources configured to emit light, and preferably the half width of the peak is 15 to 35 nm. In a more preferred embodiment of this aspect of the invention, the light has a discontinuous spectrum with peaks at wavelengths in the range of 510-530 nm, 650-670 nm, and 770-790 nm.

  In a preferred embodiment of the light emitting device according to the present invention, the one or more light sources emit the wavelength peaks in the one or more light rays simultaneously or sequentially so as to irradiate the surface of the skin. It is configured.

  In another preferred embodiment of the light emitting device according to the present invention, the one or more light sources are one or more having a discontinuous spectrum with peaks at 520 nm, 660 nm and 780 nm and half-widths of 15 to 35 nm. It is configured to emit light.

  In a further preferred embodiment of the light emitting device according to the invention, said one or more light sources emit LEDs, preferably a first LED set to emit 520 nm light, and 660 nm light. It is provided in the form of a second LED set and a third LED set to emit light at 780 nm.

  In a further preferred embodiment of the light-emitting device according to the present invention, the device emits one or more rays having a discontinuous spectrum with peaks at wavelengths in the range of 510-536 nm, 650-670 nm and 768-792 nm. A discontinuous spectrum comprising at least three light sources, preferably having a full width at half maximum of 15 to 35 nm or having peaks at wavelengths of 510 to 536 nm, 650 to 670 nm and 768 to 792 nm Comprising at least three light sources configured to emit one or more rays of light, preferably the half width of the peak is 15 to 35 nm.

  In a further preferred embodiment of the light-emitting device according to the invention, the device comprises a single light source configured to emit simultaneously a combination of peaks at wavelengths in the range of 510-536 nm, 650-670 nm and 768-792 nm. Preferably, the half-width of said peak is 15-35 nm, optionally by removing a range of unwanted wavelengths using a series of blocking filters, or requiring three wavelength ranges By using a single light source configured to subsequently change its emission spectrum between combinations.

  In a preferred embodiment of the light emitting device according to the present invention, the device further comprises a dispenser adapted for topical application of skin care active ingredients or pharmaceutical ingredients before, during or after irradiation of the skin by the apparatus. Preferably, the skin care active ingredient is an antioxidant, carotenoid, flavonoid, polyphenol, estrogen, vitamin, peptide, palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate-methionine-glutamine-arginine -Arginine, tripeptide copper glycine-histidine-lysine, hydroxy acid, sugar amine, ceramide, metal, mineral, monoethanolamine, diethanolamine, sodium laureth sulfate, retinoid, trans-retinoic acid, hyaluro Acid, triethanolamine, resveratrol, plant extracts, algae extracts, plant molecules, polysaccharides, hydroquinone, selected from dipalmitoyl hydroxyproline (DPHP) and humectants.

In another aspect, the present invention provides a skin care active ingredient for use in the prevention, reduction and / or treatment of skin related diseases by phototherapy, wherein the use by phototherapy comprises:
Irradiating the subject's skin with one or more rays having a discontinuous spectrum having peaks at wavelengths in the range of 510-536 nm, 650-670 nm, and 768-792 nm, preferably half of the peak A value range of 15 to 35 nm, and the skin is irradiated at the above wavelength simultaneously or sequentially;
Applying the above skin care active ingredient to the skin,
The step of irradiating is performed before, simultaneously with, or after the step of applying the skin care active ingredient to the skin.

  In a more preferred embodiment of this aspect of the invention, the light has a discontinuous spectrum with peaks at wavelengths in the range of 510-530 nm, 650-670 nm, and 770-790 nm.

  In a preferred embodiment of the skin care active ingredient for use according to the invention, the light has a discontinuous spectrum with peaks at 15-35 nm half-width at wavelengths of 520 nm, 660 nm and 780 nm, preferably The light is preferably emitted by a plurality of LED light sources, more preferably a first LED set to emit 520 nm light, a second LED set to emit 660 nm light, and 780 nm light. And a third LED set to emit.

  In another preferred embodiment of the skin care active ingredient for use according to the invention, the above use by phototherapy comprises the use of a light emitting device according to the invention.

  In a further preferred embodiment of the skin care active ingredient for use according to the invention, the skin care active ingredient is an antioxidant comprising carotenoids, flavonoids and polyphenols; estrogens; vitamins and their derivatives; palmitoyl-lysine-threonine- Peptides including threonine-lysine-serine, acetyl-glutamate-glutamate-methionine-glutamine-arginine-arginine and tripeptide copper glycine-histidine-lysine; hydroxy acid; sugar amine; ceramide; metal; mineral; monoethanolamine; Sodium laureth sulfate; retinoids such as trans-retinoic acid; hyaluronic acid; triethanolamine; resveratrol; plant or algae extract containing plant molecules such as polysaccharides; Droquinone; mequinol; kojic acid; arbutin; mulberry; blueberry; cranberry; licorice; glycyrrhizinate; glabrizine; Dulse; Nagabagishigishi; Tandin; Saxifraga salmentosa; Clara; Hydroxypropyltetrahydropyrantriaol; Ferulic acid; Phloretin; Willow languinea; Niacimide; Glucosamine; Resorcinol; Peptide 51); azelaic acid; lactic acid; phytic acid; salicylic acid; trichloro acid; enzyme such as papain, bromelain; Palmitoyl hydroxyproline (DPHP); whitening component; whitening component; skin friction agents; Kozakasayaku; and is selected from humectants.

In another aspect, the present invention provides DPHP for use in a method of treating a skin-related disease, wherein DPHP is administered locally before, during and / or after phototherapy, as described above by phototherapy. Use
Irradiating the subject's skin with one or more rays having a discontinuous spectrum having peaks at wavelengths in the range of 510-536 nm, 650-670 nm, and 768-792 nm, preferably half of the peak A value range of 15 to 35 nm, and the skin is irradiated at the above wavelength simultaneously or sequentially;
Applying the above skin care active ingredient to the skin,
The above step of irradiating is performed before, simultaneously with or after the step of applying the above skin care active ingredient to the skin, preferably after the step. In a more preferred embodiment of this aspect of the invention, the light has a discontinuous spectrum with peaks at wavelengths in the range of 510-530 nm, 650-670 nm, and 770-790 nm.

  In a preferred embodiment of DPHP for use according to the invention, the light has a discontinuous spectrum with peaks at 15-35 nm half-width at wavelengths of 520 nm, 660 nm and 780 nm, preferably The light is emitted by a plurality of LED light sources, more preferably a first LED set to emit 520 nm light, a second LED set to emit 660 nm light, and 780 nm light. Provided by a third LED set to:

  In another preferred embodiment of DPHP for use according to the invention, the above use by phototherapy comprises the use of a light emitting device according to the invention.

  In a further preferred embodiment of DPHP for use according to the invention, the skin-related diseases are acute skin wounds, chronic skin wounds such as skin ulcers, pressure ulcers, diabetic skin ulcers, hypertrophic scars, scar keloids, capillaries (Spider veins), skin atrophy, precancerous skin lesions, herpes, inflammatory acne, acne vulgaris, comedogenic or polymorphic acne, nodular cystic acne, confluent Acne, senile acne, and secondary acne (sunlight, medicinal or occupational acne, etc.), ichthyosis, ichthyosis-like condition, Darier's disease, palmokeratoderma, leukoplakia and leukosis-like condition Or lichen and lichen planus, psoriasis of the skin, mucous membranes or nails, psoriatic rheumatism, skin atopy including eczema, dry skin, skin irritation, redness, sun erythema, actinic keratosis, skin allergies and allergies Or irritation contact dermatitis, atopic dermatitis, rosacea Lupus erythematosus, benign pigmented lesions are selected from the group formed by (sunlight lentigines, actinic lentigines, freckles, spots, etc. brown).

In another aspect, the present invention provides a skin care active composition for use in a method of treating a skin related disorder, wherein the composition is administered topically before, during and / or after phototherapy. The above use by phototherapy,
Irradiating the subject's skin with one or more rays having a discontinuous spectrum having peaks at wavelengths in the range of 510-536 nm, 650-670 nm, and 768-792 nm, preferably half of the peak A value range of 15 to 35 nm, and the skin is irradiated at the above wavelength simultaneously or sequentially;
Applying the above skin care active composition to the skin,
The step of irradiating is performed before, simultaneously with or after the step, preferably after the step of applying the skin care active composition to the skin. In a more preferred embodiment of this aspect of the invention, the light has a discontinuous spectrum with peaks at wavelengths in the range of 510-530 nm, 650-670 nm, and 770-790 nm.

  In another aspect, the present invention provides phototherapy skin care comprising irradiating a subject's skin with light having a discontinuous spectrum peaking at wavelengths in the range of 510-536 nm, 650-670 nm, and 768-792 nm. A half-width of the above-mentioned peak is preferably 15 to 35 nm, and the above-mentioned skin is irradiated simultaneously or continuously at the above-mentioned wavelength. In a more preferred embodiment of this aspect of the invention, the light has a discontinuous spectrum with peaks at wavelengths in the range of 510-530 nm, 650-670 nm, and 770-790 nm.

  In a preferred embodiment of the cosmetic method for providing skin care according to the present invention, the light has a discontinuous spectrum with peaks at 15-35 nm half-width at wavelengths of 520 nm, 660 nm and 780 nm, preferably The light is more preferably by a plurality of LED light sources, a first LED set to emit 520 nm light, a second LED set to emit 660 nm light, and 780 nm And a third LED configured to emit light.

  In another preferred embodiment of the cosmetic method for providing skin care according to the present invention, the phototherapy described above comprises the use of a light emitting device according to the present invention.

  In a preferred embodiment of the cosmetic method for providing skin care according to the invention, the method further comprises the application, preferably topical application, of the skin care active ingredient before, during or after the step of irradiating the skin. Preferably, the skin care active ingredient is an antioxidant comprising carotenoids, flavonoids and polyphenols; estrogens; vitamins and their derivatives; palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate-methionine- Peptides containing glutamine-arginine-arginine and tripeptide copper glycine-histidine-lysine; hydroxy acids; sugar amines; ceramides; metals; minerals; monoethanolamines; Retinoids such as neonic acid; hyaluronic acid; triethanolamine; resveratrol; plant or algae extract containing plant molecules such as polysaccharides; hydroquinone; mequinol; kojic acid; arbutin; mulberry; blueberry; cranberry; Salt; Grabrizine; Pycnogenol; Pine Spina Star; Yucan; Ascofilm Nodomus; Aspergillus Fermented; Ferla Fetida; Triol; ferulic acid; phloretin; willow lantern; niacimide; glucosamine; resorcinol; peptide (nanopeptide 1, oligopeptide 68, oligopeptide 34 Oligopeptide 51); Azelaic acid; Lactic acid; Phytic acid; Salicylic acid; Trichloroic acid; Enzymes such as papain, bromelain; Dipalmitoylhydroxyproline (DPHP); Whitening component; Whitening component; Skin friction agent; And humectants.

  In a further preferred embodiment of the cosmetic method for providing skin care according to the invention, the fluence or output (irradiation amount) provided to the skin by the irradiation is collagen in the skin as compared to the standard skin. And / or induces the production of elastin and / or induces activation, proliferation and / or cell migration of keratinocytes, fibroblasts, primordial myofibroblasts and / or myofibroblasts in said skin Enough to do.

  In a further preferred embodiment of a cosmetic method for providing skin care according to the present invention, the method comprises skin rejuvenation, skin moisturization and / or tension, surface and deep skin repair, skin tightening, filling, shaping. And wrinkle removal, eye contour improvement, skin shine enhancement and / or resulting Providing prevention, reduction and / or treatment of chronic or light-damaged skin, dry skin, hyperpigmented skin, flaccid skin, skin redness, leather-like skin, photoelastic fibrosis and alopecia.

  In another aspect, the invention provides skin by phototherapy comprising irradiating a subject's skin with light having a discontinuous spectrum that peaks at wavelengths in the range of 510-536 nm, 650-670 nm, and 768-792 nm. A method for treating a related disease is provided, preferably the half width of the peak is 15-35 nm and the skin is irradiated at the above wavelength simultaneously or sequentially. In a more preferred embodiment of this aspect of the invention, the light has a discontinuous spectrum with peaks at wavelengths in the range of 510-530 nm, 650-670 nm, and 770-790 nm.

  In a preferred embodiment of the method for treating skin-related diseases by phototherapy according to the invention, the light has a discontinuous spectrum with peaks at half-widths of 15 to 35 nm at wavelengths of 520 nm, 660 nm and 780 nm. Preferably, the light is by a plurality of LED light sources, more preferably a first LED set to emit 520 nm light and a second LED set to emit 660 nm light. And a third LED set to emit light at 780 nm.

  In another preferred embodiment of the method for treating skin related diseases by phototherapy according to the present invention, the above described phototherapy comprises the use of a light emitting device according to the present invention.

  In a further preferred embodiment of the method for treating skin-related diseases by phototherapy according to the invention, the method comprises the application of a topical pharmaceutical ingredient, preferably before, during or after the step of irradiating the skin, preferably Further comprising topical application, preferably the topical pharmaceutical ingredients are antioxidants comprising carotenoids, flavonoids and polyphenols; estrogens; vitamins and their derivatives; palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate Peptides containing glutamate-methionine-glutamine-arginine-arginine and tripeptide copper glycine-histidine-lysine; hydroxy acids; sugar amines; ceramides; metals; minerals; monoethanolamines; -Retinoids such as retinoic acid; hyaluronic acid; triethanolamine; resveratrol; plant or algal extracts containing plant molecules such as polysaccharides; hydroquinone; mequinol; kojic acid; arbutin; mulberry; blueberry; cranberry; Acid salt; glabrizine; pycnogenol; pina spina star; yukan; ascofilm nodomus; aspergillus fermented material; Pyranthriaol; Ferulic acid; Phloretin; Willow lantern; Niacimide; Glucosamine; Resorcinol; Peptide (Nanopeptide 1, Oligopeptide 68, Oligopeptide 34, oligopeptide 51); azelaic acid; lactic acid; phytic acid; salicylic acid; trichloric acid; enzyme such as papain, bromelain; dipalmitoylhydroxyproline (DPHP); whitening ingredient; whitening ingredient; skin friction agent; Selected from drugs; and humectants.

  In a further preferred embodiment of the method for treating skin-related diseases by phototherapy according to the present invention, the fluence or power (irradiation amount) brought about by the irradiation by the phototherapy on the skin is compared with standard skin. Sometimes induces the production of collagen and / or elastin in the skin and / or activation, proliferation of keratinocytes, fibroblasts, primordial myofibroblasts and / or myofibroblasts in the skin And / or sufficient to induce cell migration.

  In a further preferred embodiment of the method for treating skin related diseases by phototherapy according to the invention, the skin related diseases are acute skin wounds, chronic skin wounds such as skin ulcers, pressure ulcers, diabetic skin ulcers, hypertrophic scars. , Scar keloid, telangiectasia (spider veins), skin atrophy, precancerous skin lesions, herpes, inflammatory acne, acne vulgaris, comedogenic or polymorphic acne, nodular cyst Acne, congenital acne, senile acne, and secondary acne (such as sunlight, drug or occupational acne), ichthyosis, ichthyosis-like condition, Darier's disease, palmokeratoderma, After vitiligo and vitiligo-like conditions or lichen and lichen planus, psoriasis of the skin, mucous membranes or nails, psoriatic rheumatism, skin atopy including eczema, dry skin, skin irritation, dermatological and / or cosmetic treatment Skin irritation, skin irritation caused by radiation therapy, Skin sensation, redness, erythema of the skin, actinic keratosis, photosensitivity black, sunflower, freckles, brown spots, melanosis, radiation dermatitis, skin allergy and allergic or irritant contact dermatitis, atopic Selected from the group formed by dermatitis, rosacea and lupus erythematosus.

It is a figure which shows the phenomenon of the crosstalk between a keratinocyte and a fibroblast. FIG. 1 illustrates the interaction between keratinocytes and fibroblasts in the subject's skin. The importance of crosstalk is apparent from the situation where fibroblast differentiation is inhibited when either keratinocytes or fibroblasts are absent or abundance is reduced. As a result, the deposition of connective tissue constituents such as collagen and elastin is impaired. It is a graph which shows the influence of the fluence of irradiation with respect to wound healing in the cell culture model of a human epidermal keratinocyte illustrated in Example 1. FIG. Irradiation at different wavelengths is shown in panels A (520 nm), B (660 nm) and C (780 nm). Illumination of human epidermal keratinocytes (HEK) (panel A) and human dermal fibroblasts (FPH) (panel B) exemplified in Example 2 with a combination of 3 LEDs set at wavelengths 520, 660 and 780 nm and It is a graph which shows the result of irradiation by each LED individually. From FIG. 3, it can be seen that the combination of wavelengths shown results in increased wound healing compared to illumination with LEDs set to emit individual wavelengths of light or not to irradiate at all (CTRL). it is obvious. The particular combination of 520 nm, 660 nm and 780 nm has a better photobiological modulating effect on both keratinocytes and fibroblasts than each single wavelength. Faster experimental wound closure is observed compared to the control and also compared to each single wavelength (780 or 660 or 520 nm). FIG. 4 is a graph showing that DPHP combined with 3LED irradiation disclosed herein has a beneficial effect on skin wound healing. The experiment was performed as described in Example 3 using keratinocytes. The control is a control experiment using Dulbecco's modified Eagle medium; the serum is a control experiment using serum containing DPHP as a skin care active ingredient. The serum in this example comprises a vesicle vector loaded with DPHP, wherein the amount of DPHP in the serum is about 0.001 to 10% by weight, preferably about 0.03 to 5% by weight, based on the weight of the serum. Including to be. 3LED + serum is a test experiment using 3LED irradiation in the presence of serum; 3LEDs alone is a test experiment using 3LED irradiation in the absence of serum. It is a graph which shows the collagen production induced by 3LED irradiation. The graphical representation shows type III collagen production per fibroblast (type III collagen measured per cell nucleus) applied together with irradiation with three distinct wavelengths and serum as described in Example 4. It shows the combined effect on the amount expressed in arbitrary units. CTRL is a control experiment using Dulbecco's modified Eagle medium; CTRL + serum is DMEM with serum containing DPHP in an amount of 0.03-5% by weight; 3LEDs + serum is in an amount of 0.03-5% by weight Illumination of LEDs with three wavelengths of 520, 660 and 780 nm during cell culture in DMEM with serum containing DPHP. The y-axis shows the amount of type III collagen / cell. FIG. 5 is a graph showing the results of a wound healing comparison experiment in which different wavelength combinations were tested in comparison to wavelengths found to produce the effects described herein. The control wavelength combination was provided by a 3LED illumination system set to emit light at 590 nm (yellow / orange light), 635 nm and 735 nm. Other parameters such as light intensity and voltage were kept essentially constant. FIG. 6 shows irradiation of keratinocytes with 3 LEDs and individual LEDs, FIG. 7 shows irradiation of fibroblasts with 3 LEDs and individual LEDs, and CTRL in FIGS. 6 and 7 shows no irradiation. The results show that wound healing is not advantageously increased with the different combinations of the three wavelength ranges that do not correspond to the combination of the present invention compared to the control (no irradiation). An alternative combination of three wavelengths using a combination of 590 nm, 635 nm and 735 nm LEDs has no photobiological modulating effect on keratinocytes or fibroblasts, compared to the control and each Similar experimental wound closure is observed when compared to a single wavelength (590 nm or 635 nm or 735 nm). FIG. 5 is a graph showing the results of a wound healing comparison experiment in which different wavelength combinations were tested in comparison to wavelengths found to produce the effects described herein. The control wavelength combination was provided by a 3LED illumination system set to emit light at 590 nm (yellow / orange light), 635 nm and 735 nm. Other parameters such as light intensity and voltage were kept essentially constant. FIG. 6 shows irradiation of keratinocytes with 3 LEDs and individual LEDs, FIG. 7 shows irradiation of fibroblasts with 3 LEDs and individual LEDs, and CTRL in FIGS. 6 and 7 shows no irradiation. The results show that wound healing is not advantageously increased with the different combinations of the three wavelength ranges that do not correspond to the combination of the present invention compared to the control (no irradiation). An alternative combination of three wavelengths using a combination of 590 nm, 635 nm and 735 nm LEDs has no photobiological modulating effect on keratinocytes or fibroblasts, compared to the control and each Similar experimental wound closure is observed when compared to a single wavelength (590 nm or 635 nm or 735 nm). 520nm (151W / ^{m 2} i.e. 0.45J ^/ cm 2), configured to emit light of 660nm (224W / ^{m 2} i.e. 0.67J / cm ²⁾ or 780nm (42W / ^{m 2} i.e. 0.13J / cm ²⁾ It is a table | surface which shows the increase of the type III collagen in the dermis by the daily irradiation by 2 times of standard output (irradiation amount) for 15 seconds compared with the case of 1 time of irradiation for 15 seconds by LED made. Based on 7 days, the irradiation dose includes 3.2 J / cm ² (520 nm), 4.7 J / cm ² (660 nm) and 0.89 J / cm ² (780 nm), and the total of all 3 LEDs is 8.8 J / Cm ² . Type III collagen increased by 339% when irradiated twice for 15 seconds. In some preferred embodiments in aspects of the invention, the output (irradiation dose) ranges are, for example, 113-189 W / m ² for irradiation of LEDs emitting 520 nm and 168-280 W / m for LEDs emitting 660 nm. Note that for LEDs emitting ² or 780 nm, an output (irradiation) of 31-52 W / m ² may be included. Figures 9A-9D show an exemplary embodiment of an apparatus according to the present invention. Refer to other sections of this specification for a detailed description. It should be understood that the device according to the present invention may take the form of a device having a movable applicator as disclosed in WO 2014/091035 and WO 2015/193303 in one embodiment. The disclosures of which are hereby incorporated by reference in their entirety. It is a graph of the keratinocytes irradiated with LED light of 520, 660, and 780 nm described in Example 6. LEDs with a wavelength of 520 nm have a photobiological modulating effect on keratinocytes and show faster experimental wound closure compared to controls. FIG. 6 is a graph of fibroblasts irradiated with LED light of 520, 660, and 780 nm described in Example 6. LEDs with a wavelength of 520 nm have no photobiological modulating effect on fibroblasts and a similar experimental wound closure profile is observed compared to controls. FIG. 6 is a graph showing wound closure by fibroblasts in the supernatant obtained from culture of keratinocytes irradiated with 520, 660, 780 nm LED light as described in Example 6. It is clear that the photobiological modulating effects of 520 nm LEDs on keratinocytes induces fibroblast migration and faster experimental wound closure in fibroblast cultures. This is considered to indicate a phenomenon in which keratinocytes secrete activators for fibroblasts in response to 520 nm LED irradiation. It is a graph which shows the effect with respect to the proliferation of the fibroblast of the supernatant obtained from the keratinocyte culture | cultivation when irradiated with LED light. Irradiation of a combination of 520 nm, 660 nm and 780 nm LEDs results in a photobiological modulating effect on keratinocytes, which promotes fibroblast migration and faster experiments in fibroblast cultures. Wound closure is induced. Irradiation using a combination of three wavelengths is superior to the control and each single wavelength. The keratinocytes are thought to secrete activators for fibroblasts in response to this specific 3LED combination irradiation. FIG. 9 is a graph of a comparative experiment showing the effect of keratinocyte supernatant on fibroblast migration and wound closure when irradiated at wavelengths other than 520, 660 and 780 nm as described in Example 8. FIG. 10 is a graph of keratinocytes treated (irradiated) with LEDs as described in Example 9. FIG. 10 is a graph of fibroblasts treated with LEDs as described in Example 9. 10 is a graph of supernatant of keratinocytes treated with LED against fibroblasts, as described in Example 9. FIG. FIG. 6 shows ex vivo skin irradiation results showing that the specific combination of 520 nm, 660 nm and 780 nm LEDs exemplified in Example 10 also has a photobiological modulating effect on the epidermis ex-vivo. is there. In skin explants, 3LED irradiation according to the present invention increases the thickness of the epidermis due to an increase in the epidermal cell layer. Panel A: Control; Panel B: Combination of 520 nm, 660 nm and 780 nm LEDs; Panel C: Graphic representation of epidermis thickness measurements for control and experimental conditions, showing a 24% increase upon phototherapy . It is a figure which shows that triple LED irradiation by 520 nm, 660 nm, and 780 nm LED illustrated in Example 10 has a photobiological adjustment effect | action in a skin explant. Irradiation increases the total collagen matrix protein expression (panel B) by approximately 11% compared to the control (panel A) (panel C). Panel C shows a graph of total collagen measurements for control and experimental conditions, showing an 11% increase upon phototherapy. It is a figure which shows that triple LED irradiation by 520 nm, 660 nm, and 780 nm LED illustrated in Example 10 has a photobiological adjustment effect | action in a skin explant. Irradiation increases the type III collagen matrix protein expression in explants (panel B) by a factor of 3 compared to controls (panel A) (panel C). Panel C shows a graphical representation of type III collagen measurements for the control and experimental conditions, showing a 322% increase in type III collagen in the phototherapy ex vivo skin experiment according to the present invention. Acid Glycosaminoglycan (GAG) expression in skin tissue explants of phototherapy light treatment using a specific combination of 520 nm, 660 nm and 780 nm LEDs according to the present invention (3LED) as exemplified in Example 10 It is a figure which shows the ability to induce. Figures A1 and A2 show a control (no irradiation) and show that the skin explants are not stained after Alcian Blue-PAS staining. Figures B1 and B2 show a blue staining throughout the dermis. The acid GAG is mainly composed of hyaluronic acid and is involved in dermis construction and skin tissue moisturization. FIG. 6 shows ex vivo skin irradiation results showing that the specific combination of 520 nm, 660 nm and 780 nm LEDs exemplified in Example 10 also has a photobiological modulating effect on the appearance of the dermis-epidermal junction. FIG. In skin explants, irradiation increases the density of both the dermis and the dermis at the dermis-epidermal junction (shown below is the histology in the explant photograph). A: Control (serum only); Panel B: 3 LED irradiation (520 nm, 660 nm and 780 nm LEDs); Panel C: Combination of serum application with 3 LED irradiation. 3LED irradiation provides a protective effect on the integrity of the skin dermis-skin junction and skin tissue, protecting skin explants from dermis-skin junction peeling and epidermal necrosis.

Definitions The term “light” as used herein refers to electromagnetic radiation of a particular wavelength or group of wavelengths. In the context of the present invention, the term “light” refers in particular to visible and infrared light, preferably near infrared.

  In the context of the present invention, the electromagnetic spectrum is referred to herein as including visible light and infrared light. The above spectra consist of blue-violet light (380-436 nm), blue light (436-495 nm), green light (495-566 nm), yellow light (566-589 nm), orange light (589-627 nm) and red light (627). Visible light such as (˜780 nm), as well as (ii) infrared (78 nm to 1000 nm). Infrared rays include near infrared rays (700 nm to 3000 nm).

  The term “green light” as used herein refers to light having a wavelength in the range of 495-566 nm. More preferably, the term “green light” is used herein and also when referred to as range (i), 496-565 nm, 497-564 nm, 498-563 nm, 499-562 nm, 500-561 nm, 501 -560 nm, 502-559 nm, 503-558 nm, 504-557 nm, 505-556 nm, 506-555 nm, 507-554 nm, 508-553 nm, 509-552 nm, 510-551 nm, 511-550 nm, 512-549, 512-545 nm , 512-540, 512-538 nm or 512-536 nm. Even more preferably, the light has a peak wavelength in the range of 512-536 nm, most preferably 510-530 nm. Furthermore, preferably at least 50% of the light energy emitted by the light emitting device, preferably the light source, preferably at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% is 496 to 565 nm, 497 to 564 nm, 498 to 563 nm, 499 to 562 nm, 500 to 561 nm, 501 to 560 nm, 502 to 559 nm, 503 to 558 nm 504-557 nm, 505-556 nm, 506-555 nm, 507-554 nm, 508-553 nm, 509-552 nm, 510-551 nm, 511-550 nm, 512-549, 512-545 nm, 512-540 nm, 512-538 nm, 510 ~ 530nm or 512-53 It is in the range of nm. All possible combinations of wavelength range and percentage of light energy are contemplated and are intended to be individualized in this paragraph. A person skilled in the art understands that the larger the wavelength range, the higher the proportion of light energy emitted by the light emitting device that falls within the above range, in the context of the present invention.

  The term “red light” as used herein refers to light having a wavelength in the range of 627-780 nm. More preferably, the term “green light” is used herein and also when referred to as range (i), 630-750 nm, 630-740 nm, 630-730 nm, 630-720 nm, 630-710 nm, 630 It refers to light having wavelengths in the range of ˜700 nm, 635 to 695 nm, 640 to 690 nm, 645 to 685 nm, 645 to 680 nm, 650 to 675 nm, 652 to 670 nm, and 652 to 668 nm. Even more preferably, the light has a peak wavelength in the range of 652-668 nm, most preferably 650-670 nm. Furthermore, preferably at least 50% of the light or light energy emitted by the light emitting device, preferably the light source, more preferably at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% are 630-750 nm, 630-740 nm, 630-730 nm, 630-720 nm, 630-710 nm, 630-700 nm, 635-695 nm, It exists in the range of 640-690 nm, 645-685 nm, 645-680 nm, 650-675 nm, 652-670 nm, 650-670 nm, or 652-668 nm. All possible combinations of wavelength range and percentage of light energy are contemplated and are intended to be individualized in this paragraph. A person skilled in the art understands that the larger the wavelength range, the higher the proportion of light energy emitted by the light emitting device that falls within the above range, in the context of the present invention.

  The term “near infrared” as used herein refers to a discontinuous spectrum of light having a peak at a wavelength in the range of 700 nm to 3000 nm. In other words, the above terms include, but are not exclusively related, to refer to some combination of red and infrared spectra. Preferably, the near-infrared ray is also referred to as range (iii) and is light having a wavelength in the range of 700 to 3000 nm. Even more preferred, the above terms are 710-2000 nm, 710-1500 nm, 710-1000 nm, 720-1000 nm, 725-1000 nm, 730-900 nm, 735-850 nm, 735-830 nm, 735-820 nm, 740-815 nm. 745-815 nm, 750-810 nm, 755-805 nm, 760-800 nm, 765-795 nm, 765-792 nm, or 768-788 nm. Even more preferably, the light has a peak wavelength in the range of 768-788 nm, most preferably 770-790 nm. Furthermore, preferably at least 50% of the light or light energy emitted by the light emitting device or light source, more preferably at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% , 95%, 96%, 97%, 98%, 99% or 100% is 700 to 3000 nm, 710 to 2000 nm, 710 to 1500 nm, 710 to 1000 nm, 720 to 1000 nm, 725 to 1000 nm, 730 to 900 nm, 735 850 nm, 735-830 nm, 735-820 nm, 740-815 nm, 745-815 nm, 750-810 nm, 755-805 nm, 760-800 nm, 765-795 nm, 765-792 nm, 770-790 nm or 768-788 nm . All possible combinations of wavelength range and percentage of light energy are contemplated and are intended to be individualized in this paragraph. A person skilled in the art understands that the larger the wavelength range, the higher the proportion of light energy emitted by the light emitting device that falls within the above range, in the context of the present invention.

  The term “light emitting device” as used herein refers to an electrical or electromagnetic device configured or constructed to generate or provide light of any particular wavelength or any group of wavelengths. Including. Unless otherwise specified, the light emitting device of the present invention sends or delivers the emitted light from the device in the direction of the space directly surrounding the device. The space is preferably air.

  The term “light source” as used herein refers to one or more light emitting elements or lamps that, when subjected to an electrical or electromagnetic signal, thereby emit light of any particular wavelength or group of wavelengths. Includes mention. The light source may be a laser, but the preferred light source is an LED (light emitting diode) or equivalent. The “light source” may emit light continuously or in a pulse mode. The light source used in aspects of the present invention is configured to emit light having a discontinuous spectrum that peaks in a specific range of wavelengths. The term “discontinuous spectrum” as used herein does not emit evenly across the entire color spectrum, but instead has a spike or peak at a particular wavelength and little or no emission at other wavelengths. Refers to the light source.

  The term “half-width” as used herein refers to the width of the wavelength (in nm) at half the height of the peak.

  The term “range” as used herein includes the value at the end of the range.

  The terms “sending” or “sent”, as used herein, refer to emitted light at one or more wavelengths that illuminate the subject's skin. One skilled in the art understands that the emitted light can be identical to the transmitted light in the absence of an optical filter. When an optical filter is present, the wavelength composition of the transmitted light is different from the composition of the emitted light. Unless otherwise specified in the context of the present invention, the emitted light is also light that irradiates the skin.

  The term “photobiological modulation” as used herein stimulates cells present in the skin and initiates light-induced signaling pathways, preferably by endogenous photoreceptors, thereby Refers to the use of light to bring physiological effects to the skin. For example, photobiological modulation increases keratinocyte proliferation and / or migration, and increases production of extracellular matrix proteins such as type I and / or type III collagen and elastin by fibroblasts.

  The term “subject” as used herein refers to an animal, preferably a mammal, and most preferably a human. In particular, the term “subject” relates to a mammal or a human in need of a cosmetic method according to the invention or a method for treating a skin-related disease according to the invention. Those skilled in the art will be able to apply the irradiation methods now apparent and described with respect to the subject matter of the present invention for cosmetic purposes (ie non-therapeutic purposes) and therapeutic purposes, the latter being used to treat illnesses or diseases or Understand what is related to prevention. When referring to the term phototherapy, as used herein, no particular limitation is intended for either cosmetic or medical methods. In embodiments of the invention, the subject may be a mammal, preferably a human. When the skin is hairy, it is preferably treated by shaving, for example, before irradiation of the skin, so that light can strike and penetrate the skin.

  The term “skin” refers to, but is not limited to, the outer covering of the vertebrate in any part of the subject's body, including but not limited to the face, neck, chest skin, abdomen, back, Includes arm, axilla, hand, buttocks, leg skin, and / or scalp. The term “skin” includes epidermal tissue, dermal tissue and / or subcutaneous tissue.

  The phrase “irradiate the skin” or any form thereof, as used herein, refers to applying light to the surface of the skin. Preferably, the irradiation of the skin is performed by a light emitting device that is placed outside the body and emits light that penetrates (i) the epidermis, (ii) the epidermis and dermis, or (iii) the epidermis, dermis and subcutaneous. The phrase “the skin is illuminated simultaneously or sequentially by the above wavelengths” means light from any one of the above three wavelengths of green, red and near infrared as defined herein. Refers to simultaneous or sequential irradiation. Preferably, the irradiation is simultaneous with light from the three wavelengths.

  As used herein, “beauty” refers to the appearance of skin tissue, which seems to preserve, repair, bring about or enhance the beautiful appearance on the body, or enhance beauty or youthfulness. , Refers to a beautifying substance or handling process.

  As used herein, the term “beauty effective amount” is sufficient to treat one or more signs of skin aging, but low enough to avoid serious side effects such as permanent scarring. Means the amount of irradiation by skin care active ingredient, composition or phototherapy. The cosmetically effective amount of the skin care active ingredient, composition or irradiation depends on the particular condition being treated, the age and physical condition of the subject, the severity of the condition being treated or prevented, the duration of the treatment, the other treatment being used, the particular Depending on the nature of the active skin care ingredients or product / composition of the skin, as well as similar factors. Preferably, the cosmetic method according to the present invention provides a cosmetically effective amount of irradiation and / or skin care active ingredients to the skin of the subject.

  As used herein, the term “therapeutically effective amount” is sufficient to treat one or more signs of a skin disorder, but low enough to avoid serious side effects such as permanent scarring. Means the amount of irradiation by skin care active ingredient or pharmaceutical ingredient, composition or phototherapy. The therapeutically effective amount of an active ingredient, preferably a skin care active ingredient or pharmaceutical ingredient, composition or radiation, is the specific disease being treated, the age and physical condition of the subject, the severity of the disease being treated or prevented, the duration of treatment, It depends on the other treatments used, the nature of the particular compound or product / composition, and similar factors. Preferably, the method for treatment according to the invention or the DPHP for use according to the invention provides a therapeutically effective amount of irradiation and / or skin care or pharmaceutical ingredients to the skin of the subject.

In order to obtain a therapeutically effective amount or a cosmetically effective amount in the method of the present invention (this amount is preferably expressed in W / m ² as output (sometimes referred to herein as radiation dose)) The step of irradiating the surface of is performed at an output (irradiation amount) sufficient to induce the production of collagen and / or elastin by skin cells in specific fibroblasts. In addition or alternatively, the step of irradiating the surface of the skin induces activation, proliferation and / or cell migration of keratinocytes, fibroblasts, primordial myofibroblasts and / or myofibroblasts It is carried out with a sufficient output (irradiation amount). In order to determine whether the output (irradiation dose) is sufficient to induce the production, activation, proliferation and / or cell migration described above, for example, as described in Examples below, keratinocytes or fibers Appropriate tests can be performed in blast cell culture.

  The term “cosmetic method” as used herein refers to a method for cosmetic or aesthetic purposes. The cosmetic methods of the present invention include treatments that are non-therapeutic in nature, have no medical need and do not involve substantial physical intervention on the body to maintain the life and health of the subject. It is only intended to do. The cosmetic method of the present invention comprises the reduction of connective tissue fibers of the skin, such as collagen and / or elastin, preferably related to age-related or UV exposure, and / or the production of myofibroblasts and myofibroblasts. Prevent, reduce, treat and / or eliminate any skin phenotype characterized by having a reduction. In the context of the present invention, such skin phenotypes are, for example, wrinkles, scars or scarring, cellulite, yellowed skin, chronic or light-damaged skin, dry skin, hyperpigmented skin, flaccid skin Leather-hard skin, photoelastic fibrosis and alopecia. It is clear that the cosmetic method of the present invention meets the needs of healthy subjects who want improved cosmetic and aesthetic appearance.

  The (topical) composition used in embodiments of the present invention preferably further comprises a dermatologically acceptable carrier. As used herein, the phrase “dermatologically acceptable carrier” refers to an active ingredient that is suitable for topical application to the skin, has good aesthetic properties, and is used in embodiments of the present invention and Meaning that it is compatible with any other component and does not cause any safety or toxicity concerns. The compositions of the present invention may comprise from about 50% to about 99.99% dermatologically acceptable carrier, alternatively from about 60% to about 99.9% carrier, from about 70% to about 98% carrier, or alternatively About 80% to about 95% of the carrier.

  Dermatologically acceptable carriers can be in a wide variety of forms. Non-limiting examples include simple solutions (aqueous or oily), solid forms (eg gels or sticks) and emulsions. As used herein, an “emulsion” generally includes an aqueous phase and a lipid or oil. Lipids and oils may be derived from animals, plants or petroleum and may be natural or synthetic. Emulsion carriers include, but are not limited to, oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone emulsions. In one embodiment, dermatologically acceptable carriers include oil-in-water emulsions and water-in-oil emulsions. In yet another embodiment, the dermatologically acceptable carrier is an oil-in-water emulsion.

  The term “skin care”, in the context of the present invention, refers to the use of phototherapy or combination therapy as indicated herein to produce a cosmetic or therapeutic effect on the skin and induces the production of collagen and / or elastin. And / or inducing keratinocytes, fibroblasts, primordial myofibroblasts and / or myofibroblasts activation, proliferation and / or cell migration, Provide prevention, reduction, treatment and / or elimination of one or more of the skin related disorders. Preferably, skin care includes skin rejuvenation, skin moisturization and / or tension, deep skin repair, skin tightening and wrinkle removal, eye contour improvement, skin shine enhancement and wrinkles, fine lines, senile plaques, Scars, stretch marks, cellulite, yellowed skin, swollen eyes, dark circles, chronic or light-damaged skin, dry skin, hyperpigmented skin, flaccid skin, redness of the skin, skin as hard as leather Prevention and / or reduction and / or treatment of photoelastic fibrosis and alopecia.

  The term “phototherapy” is used herein as a generic term to refer to any method of irradiating the skin with light for therapeutic or cosmetic purposes.

The term “fluence”, as used herein, also commonly referred to as radiant exposure, is a unit of measure (output (irradiation dose) W for the amount of light energy delivered per unit area of skin over a predetermined amount of time. / M ² × time (seconds)) and is expressed in J / m ² . Regarding the content of the present invention, the output (irradiation amount) is preferably expressed in W / m ² . One skilled in the art readily understands that the output (dose) depends on the current, voltage and the specific effectiveness of the LED or LED (s). Those skilled in the art will readily understand that the fluence depends on the current, voltage, irradiation time, distance between the skin and the irradiation device, and the unit area irradiated. The output (irradiation amount) is adjusted by adjusting an appropriate setting of the light emitting device, such as a voltage. Furthermore, the distance (irradiation amount) can be adjusted by adjusting the distance to the irradiated portion. In the cosmetic or therapeutic method according to the present invention, the output (irradiation amount) provided to the skin preferably induces the production of collagen and / or elastin in the skin and / or keratinocytes in the skin, It is sufficient to induce activation, proliferation and / or cell migration of fibroblasts, primordial myofibroblasts and / or myofibroblasts. Such output (irradiation dose) is preferably measured in a cell culture of keratinocytes or fibroblasts. The distance between the light emitting device and the skin is preferably less than 10 cm, more preferably less than 5 cm, more preferably less than about 3 cm. Most preferably, the light emitting device is in direct contact with the skin such that the portion of the skin to be treated is directly irradiated. The distance between the skin and the light source of the light emitting device is preferably less than 30 cm, more preferably less than 20 cm, more preferably less than 10 cm, more preferably less than 5 cm, and in some embodiments preferably from the skin surface. About 0.05-29 mm, and in alternative or embodiments, preferably in contact with the skin. In the context of the present invention, treatment may be expressed by fluence or by power (irradiation dose).

  The term “irradiation time” as used herein refers to the time to irradiate the skin with light of any wavelength resulting from a light emitting device according to the present invention. In a simple situation, when the skin is continuously irradiated without interruption, the irradiation time can be calculated as the elapsed time between t = 0 (irradiation start) and t = x (irradiation end). In the case of an irradiation session using pulsed light, the above time is calculated by multiplying the irradiation time of one pulse by the number of pulses. One skilled in the art understands that light from other light sources, such as sunlight, is not considered in the calculation of irradiation time. In fact, in the method of the present invention, light from a light source other than the light emitting device of the present invention or light of a different wavelength is preferably blocked from reaching the skin during the irradiation time of the phototherapy according to the present invention. The The irradiation time is preferably 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 40, 45, 50, 55 or 60 seconds, more preferably 15 seconds. Most preferably, the irradiation time is a number of irradiation times, such as 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27. 28, 29, 30, 31, 32, 33, 34, 35, 40, 45, 50, 55 or 60 seconds, 2 times or more, 3 times or more, 4 times or more, preferably without irradiation At intervals, i.e. the irradiation is interrupted, 15 seconds twice. Said spacing is preferably at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 ~ 50, 51-59 or 60 seconds, or at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 minutes. In the embodiment of the present invention, the irradiation time is preferably 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28. 29, 30, 31, 32, 33, 34, 35, 40, 45, 50, 55 or 60 seconds, about 2 or more times a day, 3 times or more, preferably 4 times or more, preferably 1 day Repeat once or twice, preferably once a day, about 10 to 20 seconds, preferably 15 seconds about twice. The light provided in the cosmetic or therapeutic method according to the invention is preferably from 1 to 5 times, preferably once or twice per day, for a period of at least 3 days, preferably at least 1 week, preferably at least 4 weeks, Applicable for a maximum lifetime.

  The term “collagen” as used herein refers to any type of collagen that is produced in the skin of a subject and deposited in any form. In particular, the term “collagen” refers to type I and / or type III collagen of mammals, preferably humans.

  The term “elastin” as used herein refers to any type of elastin that is produced in the subject's skin and deposited in any form. In particular, the term “elastin” refers to mammalian, preferably human elastin.

  The term “fibroblast” is the most common cell type of connective tissue in animals and synthesizes the extracellular matrix that is the structural framework (stroma) of animal tissue. Fibroblasts in particular produce reticulated and elastic fibers such as collagen, glycosaminoglycans, hyaluronic acid, and elastin. Skin fibroblasts are cells in the dermis layer of the skin that are responsible for producing connective tissue fibers and play an important role in skin activation processes such as wound healing by restoring the skin from injury . The term also includes reference to primordial myofibroblasts and myofibroblasts. Original myofibroblasts differentiate into myofibroblasts, especially under the influence of inducing factors released from keratinocytes. (Original) myofibroblasts increase skin tension compared to fibroblasts.

  The term “keratinocytes” refers to the major cell type in the epidermis, the outermost layer of the skin. The proliferation and migration of keratinocytes plays an important role in skin activation processes such as wound healing.

  The term “standard skin” as used herein is irradiated by one or more rays that are not irradiated or that result in light that peaks at wavelengths that do not correspond to green light, red light, and near infrared. Refers to the skin, induction of collagen and / or elastin production in the skin and / or activation, proliferation and / or cells of keratinocytes, fibroblasts, primordial fibroblasts and / or myofibroblasts Induction of migration does not occur. This may be due to illumination by insufficient photons at the above wavelengths corresponding to the green light, red light and near infrared light disclosed herein, or at other wavelengths, ie the green light disclosed herein, This is for irradiation with photons at wavelengths that do not correspond to red light and near infrared. Induction of collagen and / or elastin production in the skin can be measured as an increase in production of collagen and / or elastin (respectively) by fibroblasts, as described in the experimental section later in this specification. (Expressed in arbitrary units as the amount of collagen and / or elastin measured per cell nucleus). Basically, anti-collagen (eg anti-type III procollagen) and / or anti-elastin antibodies can be used in enzyme-linked immunoassays (eg ELISA), the implementation of which is well known in the art. (Eg, Giro et al., 1981. Collagen Rel Res 15: 108). Such a test may be performed by using an appropriate control antibody. Proliferation and / or cell migration of keratinocytes, fibroblasts, primordial myofibroblasts and / or myofibroblasts, immunostaining of skin cells, video microscopy or time-lapse photography and subsequent video analysis or It can be measured by using it in combination with image analysis. Wound healing can be measured by a similar method.

  The term “wrinkle” as used herein refers to signs of skin aging associated with reduced elasticity or structural integrity in skin tissue, including but not limited to sagging tissue. , Loose and loose tissues, resulting in the presence of wrinkles including fine lines, fine wrinkles or rough wrinkles in the skin. Examples of wrinkles include, but are not limited to, wrinkles around the eyes (eg, “grass leg”), brow droop, tear troughs, and bunny lines. (Bunny lines), forehead and cheek, wrinkles between eyebrows, nasal lip groove, vertical lines of lips, marionette lines around the mouth and mental crease. Loss of elasticity or tissue structure integrity can be the result of many factors, including but not limited to illness, aging, hormonal changes, mechanical trauma, environmental damage, or cosmetics or pharmaceuticals The result of application to the organization of such products.

  The term “scar” as used herein refers to the portion of fibrous tissue (fibrosis) that replaces normal skin after injury. Scars arise from the biological process of wound healing in the skin.

  The term “cellulite”, as used herein, generally has a skin-like appearance filled with contents, generally consisting of protrusions of fatty leaflets by non-stretch connective tissue. In particular, it refers to the skin of the abdomen, thighs, and buttocks.

  The term “hyperpigmentation” as used herein refers to skin with an increased amount of melanin in the dermis or epidermis that may be caused, for example, by exposure to sunlight.

  The phrase “skin tension”, as used herein, refers to an increase in skin firmness and / or a decrease in the amount and / or extent of wrinkles.

  The term “cosmetic composition” as used herein refers to a cosmetic composition comprising an active ingredient that can be applied topically to mammalian keratinous tissue, such as human skin, among others.

  The terms “skin care active ingredient” or “pharmaceutical ingredient” are used interchangeably herein and preferably have a cosmetic or therapeutic effect on the skin, respectively (eg synthetic compounds or natural sources). Or a compound isolated from a natural extract). The skin care active or medicinal component that can be provided in the dispenser of the device or in a (disposable) capsule or in a cartridge removably connected to the device of the invention is in principle any skin care Can be an ingredient. Non-limiting examples are those set forth herein above, such as mequinol, kojic acid, arbutin, mulberry, blueberry, cranberry, licorice, glycyrrhizinate, grabrizine, pycnogenol, pina spinastar, yukan, ascofilmo Domus, Aspergillus fermented material, Ferla fetida, Mittra carpath skaver, Dutch glass, Darus, Nagabagishigishi, Tandin, Saxifraga salsa, Clara, Hydroxypropyltetrahydropyrantriaol, Ferulic acid, Phloretin, Yanagiran, Niacimide, Glucosamine, Resorcinol , Peptides (nanopeptide 1, oligopeptide 68, oligopeptide 34, oligopeptide 51), azelaic acid, lactic acid, phytic acid, salicylic acid, trichloroacid, enzyme For example, papain and bromelain) and the like. Examples of skin care active ingredients or pharmaceutical ingredients that are very suitable include antioxidants (carotenoids, flavonoids, polyphenols, etc.), hormones (estrogens, etc.), skin anti-aging agents such as green tea, bearberry leaves extract and unde. Skin whitening agents such as silenoylphenylalanine, vitamins, peptides (such as palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate-methionine-glutamine-arginine-arginine and tripeptide copper glycine-histidine-lysine) Hydroxy acids, sugar amines, ceramides, metals, minerals, monoethanolamine, diethanolamine, sodium laureth sulfate, retinoids such as trans-retinoic acid, hyaluronic acid, triethanolamine, resverato Lumpur, plant or algal extracts containing plant molecular polysaccharides such as hydroquinone, dipalmitoyl hydroxyproline (DPHP) and moisturizing agents. Skin care active ingredients or pharmaceutical ingredients are occlusive agents such as, but not limited to, petrolatum, lanolin, mineral oil, silicone and zinc oxide, as disclosed in detail in WO2005102266; E.g., but not limited to, glycerin, propylene glycol, sorbitol, hexylene glycol, butylene glycol, urea and alpha hydroxy acids; emollients such as, but not limited to, vegetable oils , Polyisobutene, squalene, fatty acids and ceramides; proteins such as, but not limited to, collagen, keratin, elastin and protein mixtures (eg wheat protein); anti-aging agents such as, but not limited to Not the grape Child extract, hydrolyzed collagen, jojoba protein, elastin, gelatin, chondroitin sulfate, oligopeptide, phytic acid, spirulina extract, PCA calcium, ceramide, corn kernel extract, DHEA, pullulan, ferulic acid, hyaluronic acid, genistein , Kojic acid, dipalmitate, yukan, coenzyme Q10, ectoine, TIMP2, L-ascorbic acid (vitamin C), alzylline, dipalmitoylhydroxyproline (DPHP), allantoin (2,5-dioxo-4-imidazolidinyl urea), retinol Palmitate (vitamin A) and provitamin B5; anti-acne agents such as, but not limited to, tretinoin, isotretinoin, adapalene, tazarotene, azelaic acid, clindamy Syn, erythromycin, tetracycline, benzyl peroxide, salicylic acid, citric acid and glycolic acid; UGT enzyme inducers such as, but not limited to, chrysin (5,7-dihydroxyflavone) and other flavonoids such as tectonic It may also include chrysin, chrysin 5-methyl ether, galangin, galangin 5-methyl ether, pinocembrin, pinobankin, apigenin, fisetin, hesperitin, kaempferol, morin, myricetin, naringenin, quercetin, quercitin, rutin and the like. CTFA Cosmetic Ingredient Handbook, Ninth Edition (2002) describes a wide variety of non-limiting cosmetic and pharmaceutical ingredients commonly used in the skin care industry, which in the aspect of the present invention are active skin care ingredients. Or it is suitable for use as a pharmaceutical ingredient. Non-limiting examples of these ingredients include healing agents, anti-aging agents, anti-wrinkle agents, moisturizers, antibacterial agents, antifungal agents, anti-inflammatory agents, anti-itch agents, anesthetics, antiviral agents, keratins Solubilizers, free radical scavengers, anti-seborrheic agents, anti-dandruff agents, anti-acne agents, skin friction agents, agents that regulate skin differentiation, proliferation or pigmentation and agents that promote penetration, skin conditioning agents Pharmaceuticals, wetting agents, softeners, antiseptics, antibacterial agents, antioxidants, enzymes, enzyme inhibitors, enzyme inducers, coenzymes, plant extracts, ceramides, peptides, topical analgesics, skin bleaching and whitening agents ( Eg hydroquinone, kojic acid, ascorbic acid, magnesium ascorbate phosphate, glucosamine ascorbate), skin conditioning agents (eg other and moisturizers such as occlusive agents), skin soothing and / or healing agents Derivatives (e.g., panthenol and derivatives (e.g., ethyl panthenol), aloe extract, pantothenic acid and its derivatives, bisabolol, and dipotassium glycyrrhizinate), and vitamins and derivatives thereof, as well as lignans. A preferred skin care active ingredient is DPHP. The skin care active ingredient is preferably selected from the group consisting of the skin care active ingredients described in this paragraph. The skin care active ingredient may be useful for the prevention, reduction or treatment of skin related diseases.

  It will be apparent to those skilled in the art that these compounds are pharmaceutical or skin care active ingredients depending on their particular use.

  The skin care active ingredient is preferably formulated in a composition for topical application to the skin. Such compositions include gels, creams, lotions, shampoos, sprays and / or serums. Unexpectedly, for example, it has been found that skin care active ingredients formulated in serum and applied topically to the subject's skin can induce skin regeneration. This phenomenon is called “biological stimulation” or “biogenic induction”. More specifically, the skin care active ingredient is preferably formulated into a composition for topical application to heal wounds and induce collagen production. Preferably, the application of the skin care active ingredient is preferably formulated into a composition for topical application and combined with irradiation of the skin with light in the method according to the invention.

  The term “skin-related disease” as used herein refers broadly to undesirable skin conditions and includes those that are not cosmetically, aesthetically or medically undesirable. The term includes reference to any undesirable condition, preferably a (medical) disease or condition, affecting or associated with the skin. Preferably, the skin-related disease is acute skin wound, chronic skin wound such as skin ulcer, pressure ulcer, diabetic skin ulcer, hypertrophic scar, scar keloid, telangiectasia (spider vein), skin atrophy, precancer Skin lesions, herpes, inflammatory acne, acne vulgaris, comedogenic or polymorphic acne, nodular cystic acne, confluent acne, senile acne, and secondary acne (Sunlight, medicinal or occupational acne etc.), ichthyosis, ichthyosis-like condition, dariosis, palmokeratoderma, vitiligo and leukoplaki-like condition or lichen and lichen planus, skin, mucous membrane or nail Psoriasis, psoriatic rheumatism, skin atopy including eczema, dry skin, skin inflammation, redness, skin erythema, actinic keratosis, skin allergy and allergic or irritant contact dermatitis, atopic dermatitis, rosacea And selected from the group formed by lupus erythematosus. Skin-related diseases include acute skin wounds, chronic skin wounds such as skin ulcers, pressure ulcers, diabetic skin ulcers, hypertrophic scars, scar keloids, telangiectasia (spider veins), skin atrophy, precancerous skin Lesions, herpes, inflammatory acne, acne vulgaris, comedogenic or polymorphic acne, nodular cystic acne, confluent acne, senile acne, and secondary acne (sunlight , Medicinal or occupational acne, etc.), ichthyosis, ichthyosis-like condition, dariosis, palmokeratoderma, vitiligo and leukoplaki-like condition or lichen and lichen planus, psoriasis of the skin, mucous membranes or nails, Psoriatic rheumatism, skin atopy including eczema, dry skin, skin irritation, skin irritation after dermatological and / or cosmetic treatment, skin irritation due to exposure to radiation therapy, sensitive skin, redness, erythema of the sun, Actinic keratosis, actinic kuroko, nikko kuroko, freckles, brown spots, melanosis, Radiation dermatitis, skin allergy and allergic or irritant contact dermatitis, atopic dermatitis, rosacea, erythematous lupus, aged skin, wrinkles, fine lines, senile plaques, scars, stretch marks, cellulite, yellowed skin, Swollen eyes, dark circles, chronic or photodamaged skin, dry skin, hyperpigmented skin, flaccid skin, redness of the skin, skin as hard as leather, photoelastic fibrosis and alopecia, preferably , Aged skin, wrinkles, fine lines, senile plaques, scars, stretch marks, cellulite, yellowed skin, swollen eyes, dark eyes, chronic or photodamaged skin, dry skin, hyperpigmented skin, flaccidity It may include any one or more of skin, skin redness, leather-like skin and photoelastic fibrosis, more preferably aged skin, wrinkles, fine lines.

  The term “skin wound” as used herein refers to skin initiated by any one of various forms, such as trauma, cut, ulcer, burn, etc., and with various features. And broadly refers to damage to the underlying tissue. The term “skin wound” encompasses wounds of varying degrees depending on the depth of the wound, such as extending to the epidermis, dermis and / or subcutaneous.

  The term “topical” as used herein refers to the direct application of a composition or active ingredient on at least one part or site of the skin.

Preferred Embodiments Phototherapy The use of light emitting diodes (LEDs) in phototherapy applications has emerged relatively recently. LED phototherapy is a safe, non-thermal and non-traumatic treatment that stimulates cell activity and function. In addition to LEDs, laser light sources, preferably lasers that provide low level laser therapy (LLLT), have been used for phototherapy. Both LED light therapy and LLLT, in contrast to high-level laser therapy (HLLT), absorb the cells, chromophores and / or photon energy that is hardly lost like heat in the tissue. Delivered directly to the photoreceptor, it can stimulate cellular activity in skin tissue.

  In preferred embodiments of aspects of the present invention, LEDs are used. The difference between laser light and LED light is that LED light emits non-coherent, quasi-monochromatic light rays. This means that, in contrast to a laser, an LED does not emit in-phase light of only one particular wavelength, but emits light in one wavelength spectrum or range. For example, an LED set to emit 632 nm light can generate 94% of its light output in light having a wavelength of 630-634 nm, whereas the corresponding laser has a wavelength of 632 nm. Only in-phase light. Those skilled in the art will recognize that an LED configured to emit light of a wavelength not within the claimed wavelength range will have one of its light outputs as light having a wavelength of light that falls within the claimed wavelength range. It is clear that the part can be brought sufficiently. Next-generation LEDs are characterized by a phenomenon called “photon interference” due to the intersection of LED energy flux from individual LEDs, which dramatically increases the intensity of photons compared to previous generation LEDs. To do.

  Currently, the biochemical mechanism of phototherapy is not precisely known. However, phototherapy can elicit intracellular biochemical reactions, so that emitted photons can be absorbed into mitochondria and membranes of photoreceptors or skin cells, such as porphyrins, flavins, and other light-absorbing components. It is known to be absorbed by molecular chromophores. The effects of phototherapy are due to activation of the mitochondrial respiratory chain component, resulting in a cascade of cellular responses in which cytochrome c oxidase plays a central role in photon absorption and biochemical signal transmission. There is a basis for what can be started.

  Fibroblasts and keratinocytes play a major role as effectors and mediators in wound healing and skin activation processes such as maintaining skin integrity, elasticity and appearance (see FIG. 1), collagen It is further known that elastin is produced. These molecules are known to have beneficial effects on skin activation processes such as wound healing and improve skin elasticity and appearance.

  Surprisingly, irradiation of keratinocytes and fibroblasts in tissue culture with specific combinations of wavelengths has a beneficial effect on the proliferation and migration of these cells, rather than irradiation with individual wavelengths. It has been found that it is further beneficial and it can have significant utility with respect to methods for improving the skin activation process such as wound healing or cosmetic methods for improving skin appearance. . It has further been found that this combination of wavelengths has a beneficial effect on the production of collagen. The higher amount of collagen has a cosmetically beneficial effect because it results in a more tense, denser and tighter skin.

  Methods for measuring cell proliferation and cell migration are known in the art and include the use of cell counters such as Coulter® counters and the use of Essen Woundmaker (Essen Bioscience), thereby confluent cell culture. Measure the time required to close the scratch.

  Methods for measuring the synthesis of different isotypes of collagen by fibroblasts, particularly type III collagen, are known in the art, such as type III collagen specific antibodies such as LS-B693 (LifeSpan (Seattle, USA)), and Includes immunohistochemical and image analysis using quantitative amplification of collagen expression products.

  The inventors have now surprisingly found that the combination of green, red and near-infrared as defined herein has a very beneficial effect on the skin. This is surprising because antagonism or synergistic effects of different wavelengths on skin cells are not easily predictable. For example, the second wavelength of light may negate the beneficial cell activation effect caused by the first wavelength of light.

  Further, the combination of yellow / orange (590 nm), orange / red (635 nm) and near infrared (735 nm) when using the green (520 nm), red (660 nm) and near infrared (780 nm) combinations according to the present invention. Does not yield the beneficial results obtained.

  In addition, this combination of 3 LEDs is not comparable to the combination of 2 LEDs of green (520 nm) and red (660 nm), green (520 nm) and near infrared (780 nm), and red (660 nm) and near infrared (780 nm). Absent. These 2LED combinations also did not necessarily give better results than each wavelength alone, as shown in the experimental results described below.

  Without wishing to be bound by any theory, we believe that we have found a mechanism by which the green (520 nm) wavelength can act on the skin. According to the experimental results provided herein, the green (520 nm) wavelength acts upon the activation of keratinocytes, and the compounds released by these keratinocytes in response to this irradiation are the fibroblasts of the skin. Stimulate or activate cells. Irradiating dermal fibroblasts with a green (520 nm) wavelength does not in itself cause a response by these fibroblasts. This finding was obtained by irradiating a cell culture of keratinocytes and contacting the separated keratinocyte supernatant with the fibroblast culture to induce fibroblast activation / migration. . Direct irradiation of fibroblasts with 520 nm light did not induce such effects.

  For example, it has further been found that the application of DPHP synergistically enhances skin vitalization by photobiological regulation. This photobiological regulation involves irradiating the subject's skin with one or more light beams, all of which have peaks at wavelengths corresponding to green light, red light and near infrared light. This results in light having a continuous spectrum and is caused by the skin being illuminated by the wavelength peaks simultaneously or sequentially.

LIGHT EMITTING DEVICE The present invention provides a device, i.e., a light emitting device for irradiating a subject's skin by phototherapy, particularly for phototherapy. The device comprises one or more light sources configured to emit light to irradiate the surface of the skin. The light in the light beam has a discontinuous spectrum having peaks at wavelengths corresponding to green light, red light, and near infrared light. Preferably, the light in the light beam is (i) 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511 or 512 nm, Preferably 512 nm, more preferably 510 nm to 566, 560, 555, 550, 545, 540, 536 nm, preferably 536 nm, more preferably up to 530 nm, (ii) 630, 635, 640, 645, 645, 650, 652 nm, preferably 652 nm, more preferably 650 nm to 780, 750, 740, 730, 720, 710, 700, 695, 690, 685, 680, 675, 670 or 668 nm, preferably 668 nm, more preferably up to 670 nm And (iii) 700 710, 720, 725, 730, 735, 740, 745, 750, 755, 760, 765 or 768 nm, preferably 768 nm, more preferably 770 nm to 3000 nm, 2000 nm, 1500 nm, 1000 nm, 900 nm, 850 nm, 830 nm, 820 nm, 815 nm , 810 nm, 805 nm, 800 nm, 795 nm, 792 nm or 788 nm, preferably 788 nm, more preferably having a discontinuous spectrum with a peak in the wavelength range up to 790 nm. All possible combinations of wavelength ranges from (i), (ii) and (iii) described in this paragraph are contemplated and are intended to be individualized. Preferably at least 50% of the light output or light energy emitted by the light emitting device according to the present invention, more preferably at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% %, 95%, 96%, 97%, 98%, 99% or 100% are (i) 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511 nm or 512 nm, preferably 512 nm, more preferably 510 nm to 566, 560, 555, 550, 545, 540, 536 nm, preferably 536 nm, more preferably up to 530 nm, (ii) 630, 635, 640, 645, 645, 650, 652 nm, preferably 652 nm, more preferred Ranges from 650 nm to 780, 750, 740, 730, 720, 710, 700, 695, 690, 685, 680, 675, 670 or 668 nm, preferably 668 nm, more preferably up to 670 nm, and (iii) 700, 710 720, 725, 730, 735, 740, 745, 750, 755, 760, 765 or 768 nm, preferably 768 nm, more preferably 770 nm to 3000 nm, 2000 nm, 1500 nm, 1000 nm, 900 nm, 850 nm, 830 nm, 820 nm, 815 nm, It is in the range up to 810 nm, 805 nm, 800 nm, 795 nm, 792 nm or 788 nm, preferably 788 nm, more preferably 790 nm. All possible combinations of wavelength range and percentage of light energy are contemplated and are intended to be individualized in this paragraph. The wavelength ranges in this aspect, including preferred embodiments of the aspects described herein, apply equally to other aspects of the invention.

  In certain embodiments of this aspect, the light source (s) are (i) 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510. One or more wavelengths ranging from 511 or 512 nm, preferably 512 nm, more preferably 510 nm to 566, 560, 555, 550, 545, 540, 536 nm, preferably 536 nm, more preferably up to 530 nm, (ii) 630 635, 640, 645, 645, 650, 652 nm, preferably 652 nm, more preferably 650 nm to 780, 750, 740, 730, 720, 710, 700, 695, 690, 685, 680, 675, 670 or 668 nm, Preferably 668 nm, more preferably 670 n One or more wavelengths in the range up to and (iii) 700, 710, 720, 725, 730, 735, 740, 745, 750, 755, 760, 765 or 768 nm, preferably 768 nm, more preferably 770 nm to 3000 nm Essentially from one or more wavelengths ranging from 2000 nm, 1500 nm, 1000 nm, 900 nm, 850 nm, 830 nm, 820 nm, 815 nm, 810 nm, 805 nm, 800 nm, 795 nm, 792 nm or 788 nm, preferably 788 nm, more preferably 790 nm May be configured to emit light of a certain wavelength. All possible combinations of wavelength ranges from (i), (ii) and (iii) described in this paragraph are contemplated and are intended to be individualized. Preferably at least 50% of the light output or light energy emitted by the light emitting device according to the present invention, more preferably at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% %, 95%, 96%, 97%, 98%, 99% or 100% are (i) 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511 nm or 512 nm, preferably 512 nm, more preferably 510 nm to 566, 560, 555, 550, 545, 540, 536 nm, preferably 536 nm, more preferably up to 530 nm, (ii) 630, 635, 640, 645, 645, 650, 652 nm, preferably 652 nm, more preferred Ranges from 650 nm to 780, 750, 740, 730, 720, 710, 700, 695, 690, 685, 680, 675, 670 or 668 nm, preferably 668 nm, more preferably up to 670 nm, and (iii) 700, 710 720, 725, 730, 735, 740, 745, 750, 755, 760, 765 or 768 nm, preferably 768 nm, more preferably 770 nm to 3000 nm, 2000 nm, 1500 nm, 1000 nm, 900 nm, 850 nm, 830 nm, 820 nm, 815 nm, It is in the range up to 810 nm, 805 nm, 800 nm, 795 nm, 792 nm or 788 nm, preferably 788 nm, more preferably 790 nm. All possible combinations of wavelength range and percentage of light energy are contemplated and are intended to be individualized in this paragraph.

  The light source in the apparatus of the present invention is further configured to emit the wavelength peak in the light beam, simultaneously or sequentially.

  The light-emitting device of the present invention is preferably an electric or electromagnetic device, preferably an electromagnetic device, and may be, for example, a battery type. Furthermore, the light emitting device according to the invention preferably sends or delivers the emitted light from the device towards the skin.

  The light emitting device may comprise or consist of at least one, more preferably at least three light sources configured to emit light having a wavelength peak in the range indicated herein above. Or at least one, and more preferably at least three light sources configured to emit light of a wavelength consisting essentially of one or more wavelengths in the ranges indicated herein above. It may be good or consist of.

  Suitable light sources contemplated herein include any type of LED (light emitting diode), such as an organic LED (OLED) or equivalent, or a laser. By LED equivalents, any light source configured to emit light having characteristics equivalent to the light emitted or generated by the LED is contemplated.

  One skilled in the art will recognize that the light in embodiments of the present invention is one wavelength or combination of wavelengths in the ranges indicated above, eg 512, 513, 514, 515, 516, 517, 518 in the range 512-536 nm. 519, 520, 521, 522, 523, 524, 525, 526, 527, 527, 528, 529, 530, 531, 532, 533, 534, 535 and / or 536 nm, or 510, 511 in the range of 510-530 nm. One or more wavelengths of 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 527, 528, 529 and / or 530nm And 652, 653, 654, 655, 656, 6 in the range of 652-668 nm 7, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668 nm, or 650, 651, 652, 653, 654, 655, 656, 657, 658, 659 in the range of 650-670 nm , 660, 661, 662, 663, 664, 665, 666, 667, 668, 669 and / or 670 nm; and 768, 769, 770, 771, 772, in the range of 768 to 788 nm; 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787 or 788, or 770, 771, 772, 773, 774, 775 in the range of 770-790 nm. , 776, 777, 778, 779, 780, 781, 82, 783, 784, 785, 786, 787, 788, 789 and / or 790 may be light consisting essentially of one or more wavelengths in a particular range, such as one or more of the wavelengths. I understand that.

  Further emitted by the apparatus to provide the necessary wavelength peaks in the aforementioned ranges, preferably in the ranges 512-536 nm, 652-668 nm and 768-788 nm, preferably 510-530 nm, 650-670 nm and 770-790 nm. The light is essentially from one or more wavelengths ranging from 512 to 536 nm, preferably from 510 to 530 nm, essentially from one or more wavelengths ranging from 652 to 668 nm, preferably from 650 to 670 nm, and Essentially consisting of one or more wavelengths in the range of 768-788 nm, preferably 770-790 nm. Providing the right wavelength combination can be achieved by using a single light source capable of emitting the required combination or wavelength range of the three wavelengths simultaneously, possibly using a series of cutoff filters to eliminate unwanted wavelengths. It is possible to subsequently change its emission spectrum by removing the range or between the required combinations of three wavelengths or wavelength ranges, so that, for example, individual ranges of wavelengths are provided in a pulsed manner. This is possible by using a single light source.

  The light emitting device according to the present invention more preferably emits 780 nm light, at least a first LED set to emit 520 nm light, at least a second LED set to emit 660 nm light. And at least a third LED set as described above. Therefore, it is preferable that the single light emitting element is set to emit light having a single wavelength distribution. A wavelength distribution thereby means at least one wavelength or group of wavelengths. The LED does not emit monochromatic light but emits quasi-monochromatic light. Such light is not of a single wavelength, but of a range of wavelengths. Such light can have a wavelength distribution or range defined as a specific percentage of light emitted within a wavelength range. One skilled in the art will understand that if a non-monochromatic light source is used, the generated light will be in a range of wavelengths if the light emitting device is “configured” to emit light of a particular wavelength. . As defined herein, diode laser light is considered monochromatic. The bandwidth of an LED (for example FWHM, i.e. full width at half maximum of 16 nm) is not as narrow as that of a diode laser (for example, FWHM is 1.5 nm for a red diode laser). The LEDs used in aspects of the present invention are preferably narrow bandwidth or narrow spectrum LEDs (bandwidth 5-50 nm). LEDs can be designed to emit a specific narrowband wavelength centered around the peak light wavelength (the highest intensity wavelength emitted from the LED). The wavelength emitted by an LED is related to the band gap energy of the semiconductor material used in its manufacture. LED color arrays can be easily purchased from the commercial market. The wavelengths reported for the context of the present invention are preferably provided using commercially available LEDs (narrow bandwidth). The reported wavelength for commercial LEDs generally refers to the peak wavelength (wavelength at maximum spectral band energy) at which the diode is set. Bandwidth is defined in the conventional manner by the width of the spectral curve measured between points in the y-axis at half maximum amplitude, also known as full width at half maximum (FWHM), ie half width (HBW). Narrow-bandwidth LEDs contain a central spectral wavelength centered around a specific value, and have an intensity on either side of the full width half maximum (FWHM) wavelength range that extends from 10 nm to 35 nm around the central spectral wavelength. It has dropped sharply. In aspects of the present invention, the wavelengths indicated herein for LEDs may refer to peak wavelengths or central spectral wavelengths.

  The half width of the peak generated at a wavelength corresponding to green light, red light, and near infrared light generated by the light emitting device according to the present invention is preferably 10 to 50 nm, more preferably 12 to 38 nm, most preferably 15 to 35 nm, Preferably it is 10-35 nm. In a further preferred embodiment of the aspect of the present invention, the half width of the peak at a wavelength corresponding to green light, red light and near infrared light produced by a light emitting device according to the present invention or used in the method of the present invention is 10-25 or 10-35 nm, preferably smaller than these, such narrow values can be obtained with higher quality LEDs. The bandwidth may also be expressed with reference to the peak wavelength +/− 5 to 25 nm when the half width is 10 to 50 nm.

  Preferably, the light source of the light emitting device or used in the embodiments of the present invention is 520 nm +/− 5 to 15 nm, 660 nm +/− 5 to 15 nm and 780 nm +/− 5 to 15 nm, preferably 520 nm +/− 10 nm, 660 nm + / One or more light sources configured to emit light having a discontinuous spectrum with peaks at wavelengths corresponding to −10 nm and 780 nm +/− 10 nm.

  Preferably, the light source of the light emitting device or used in the embodiments of the present invention comprises at least a first LED set to emit light of 520 nm +/− 5 to 15 nm, preferably 520 nm +/− 10 nm, and 660 nm + At least a second LED set to emit light of −5 to 15 nm, preferably 660 nm +/− 10 nm, and set to emit light of 780 nm +/− 5 to 15 nm, preferably 780 nm +/− 10 nm And at least a third LED.

  The LED light source used in aspects of the present invention preferably has a wavelength range of about 10-30 or 10-35, such as 15-35 or 15-20 nm around the wavelengths 520 nm, 660 nm and 780 nm indicated herein. , Providing substantially only narrow bandwidth light exclusively.

  This light may be emitted simultaneously, for example by using three separate light sources and converging these lights into a single light beam, or the light may be colored during illumination according to the invention. It may be emitted continuously so as to change.

  Preferably, the light source of the light-emitting device according to the present invention takes into consideration the half-value width of a commercially available LED, at least a first LED set to emit light of 520 nm, and at least set to emit light of 660 nm A second LED and at least a third LED set to emit light of 780 nm, and more preferably consists of these.

  The light-emitting device according to the invention (the embodiment shown in FIG. 9) is more preferably at least partially mixed or bundled with light, and the light is at least one on the skin of the subject undergoing phototherapy. Comprising light directing means configured or constructed to direct the part, wherein the mixing or bundling of the light is performed in the subject's skin and / or before the light rays irradiate the subject's skin At least occurs in the rays. More preferably, the light directing means is an integral part of the light source. The light source can be arranged in the light emitting device of the present invention so that the emitted light is focused and thus at least partially mixed or bundled. In FIG. 9, the light directing means associated with the light source (9) comprises one or more light guides 113.

  The light source (s) is preferably configured to irradiate the surface of the skin with sufficient power (irradiation dose) to induce collagen and / or elastin production by skin cells in certain fibroblasts. ing. In addition or alternatively, the light source is preferably activated, proliferated and / or keratinocytes, fibroblasts, primordial myofibroblasts and / or myofibroblasts when compared to standard skin. It is configured to irradiate the surface of the skin with an output (irradiation amount) sufficient to induce cell migration. In order to determine whether the output (irradiation dose) is sufficient to induce the production, activation, proliferation and / or cell migration described above, for example, as described in Examples below, keratinocytes or fibers Appropriate tests can be performed in blast cell culture.

  The light emitting device according to the invention is preferably a handheld device. Preferably, the apparatus comprises a housing for mounting at least one light source, preferably the housing includes a handle, a power source for supplying power to the at least one light source, and the at least one light source. Adjusting means for adjusting power, and preferably the device directs light from at least one light source to the end of the light guide and emits light to the surface of the skin. A light guide is provided.

  The light emitting device according to the present invention preferably further comprises a dispenser or cartridge removably connected to the housing, said dispenser applying a skin care active ingredient or composition to the skin before or during irradiation of the skin by the device. It can be applied locally to the surface of An embodiment of such an apparatus is shown in detail in FIG.

  The skin care active ingredient or composition that can be supplied to the dispenser of the device may in principle be any skin care active ingredient. Very suitable examples include antioxidants (carotenoids, flavonoids, polyphenols, etc.), skin anti-aging agents such as green tea, bearberry leaf extract and skin lightening agents such as undecylenoylphenylalanine, hormones (estrogens, etc.) Vitamins, peptides (such as palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate-methionine-glutamine-arginine-arginine and tripeptide copper glycine-histidine-lysine), hydroxy acids, sugar amines, ceramides, Plants containing plant molecules such as metals, minerals, monoethanolamine, diethanolamine, sodium laureth sulfate, retinoids such as trans-retinoic acid, hyaluronic acid, triethanolamine, resveratrol, polysaccharides Algae extract, hydroquinone, dipalmitoyl hydroxyproline (DPHP), allantoin (2,5-dioxo-4-imidazolidinyl urea) and moisturizing agents. Skin care active ingredients or compositions are occlusive agents such as, but not limited to, petrolatum, lanolin, mineral oil, silicone and zinc oxide, as disclosed in detail in WO2005102266; E.g., but not limited to, glycerin, propylene glycol, sorbitol, hexylene glycol, butylene glycol, urea and alpha hydroxy acids; emollients such as, but not limited to, vegetable oils , Polyisobutene, squalene, fatty acids and ceramides; proteins such as, but not limited to, collagen, keratin, elastin and protein mixtures (eg wheat protein); anti-aging agents such as, but not limited to Not the grape seed Extract, hydrolyzed collagen, jojoba protein, elastin, gelatin, chondroitin sulfate, oligopeptide, phytic acid, spirulina extract, PCA calcium, ceramide, corn kernel extract, DHEA, pullulan, ferulic acid, hyaluronic acid, genistein, Kojic acid, dipalmitate, yukan, coenzyme Q10, ectoine, TIMP2, L-ascorbic acid (vitamin C), argylline, dipalmitoylhydroxyproline (DPHP), retinol palmitate (vitamin A) and provitamin B5; Such as, but not limited to, tretinoin, isotretinoin, adapalene, tazarotene, azelaic acid, clindamycin, erythromycin, tetracycline, benzyl peroxide , Salicylic acid, citric acid and glycolic acid; UGT enzyme inducers such as, but not limited to, chrysin (5,7-dihydroxyflavone) and other flavonoids such as tectocricin, chrysin 5-methyl ether, Galangin, galangin 5-methyl ether, pinocembrin, pinobankin, apigenin, fisetin, hesperitin, kaempferol, morin, myricetin, naringenin, quercetin, quercitin, rutin and the like may be included. CTFA Cosmetic Ingredient Handbook, Ninth Edition (2002) describes a wide variety of non-limiting cosmetic and pharmaceutical ingredients commonly used in the skin care industry, which in the aspect of the present invention are active skin care ingredients. It is suitable for use as. Non-limiting examples of these skin care active ingredients include healing agents, anti-aging agents, anti-wrinkle agents, moisturizers, antibacterial agents, antifungal agents, anti-inflammatory agents, anti-itch agents, anesthetics, antiviral agents. , Keratolytic agents, free radical scavengers, anti-seborrheic agents, anti-dandruff agents, anti-acne agents, agents that regulate skin differentiation, proliferation or pigmentation and agents that promote penetration, skin conditioning agents, pharmaceuticals , Wetting agents, softeners, preservatives, antibacterial agents, antioxidants, enzymes, enzyme inhibitors, enzyme inducers, coenzymes, plant extracts, ceramides, peptides, topical analgesics, skin bleaching and whitening agents (for example, Hydroquinone, kojic acid, ascorbic acid, magnesium ascorbate phosphate, glucosamine ascorbate), skin conditioning agents (eg, other and wetting agents such as occlusive agents), skin soothing and / or healing agents Derivatives such as panthenol and derivatives (eg ethyl panthenol), aloe extract, pantothenic acid and derivatives thereof, allantoin, bisabolol, and dipotassium glycyrrhizinate, and vitamins and derivatives thereof, lignans, and combinations thereof Can be mentioned. The skin care active ingredient is preferably selected from the group consisting of the skin care active ingredients described in this paragraph.

  The light emitting device according to the present invention preferably includes means for setting the irradiation time.

The light emitting device according to the present invention preferably has (i) an output (irradiation amount) of 130 to 200 or an output (irradiation) for a light source having a discontinuous spectrum having a peak in a wavelength corresponding to green light (range (i)). Amount) 90-150 W / m ² , more preferably 140-150 or 110-133 W / m ² , most preferably about 151 or 121 W / m ² , and (ii) a wavelength corresponding to red light (range (ii)) For a light source having a discontinuous spectrum with a peak at 100-300 W / m ² , more preferably 215-130 or 160-195 W / m ² , most preferably about 224 or 177 W / m ² , (Iii) For a light source having a discontinuous spectrum with a peak in the wavelength corresponding to the near-infrared (range (iii)), the output (irradiation amount) 20-60, Or 20 to 50 W / m ² , more preferably 40 to 50 or 30 to 40 W / m ² , most preferably about 42 or 34 W / m ² .

The light-emitting device according to the present invention preferably has (i) a fluence (radiant exposure) of 0.05 to 1 J / cm for a light source having a discontinuous spectrum having a peak at a wavelength corresponding to green light (range (i)). ² , more preferably 0.1 to 0.4 J / cm ² , most preferably about 0.36 J / cm ² , and (ii) a discontinuous spectrum having a peak at a wavelength corresponding to red light (range (ii)) A light source having a fluence (radiation exposure) of 0.05 to 1 J / cm ² , more preferably 0.4 to 0.7 J / cm ² , most preferably about 0.53 J / cm ² , (iii) a light source having a discontinuous spectrum having a peak at a wavelength corresponding to the infrared (range (iii)), the fluence (radiant exposure) 0.05~1J / cm ^2, more preferably 0.05~0.2J cm ^2, and most preferably about 0.10J / cm ^2,. The above doses may be applied in other aspects of the invention. Although the dose is per day, it may be expressed as a weekly dose (fluence). As a suitable fluence as a radiation exposure amount or a radiation energy received by the surface per unit area on the basis of one week, a wavelength range having a peak at 520 nm is 2.5 to 3.2 J / cm ² and 660 nm. The wavelength range having a peak is 3.7 to 4.7 J / cm ² , and the wavelength range having a peak at 780 nm is 0.7 to 1.0 J / cm ² . Preferably, the total fluence, when used together or apply the three illumination wavelength (e.g. 3LED), may be 6.9J / cm ² or 8.8J / cm ^2.

  With respect to embodiments according to the present invention, the distance between the light emitting device and the skin is more preferably less than 10 cm, more preferably less than 5 cm, more preferably less than about 3 cm. Most preferably, the light emitting device is in direct contact with the skin such that the portion of the skin to be treated is directly irradiated. The distance between the skin and the light source of the light emitting device is preferably less than 30 cm, more preferably less than 20 cm, more preferably less than 10 cm, more preferably about 0.05 to 29 mm from the skin surface, most preferably direct contact (0 cm ).

  With respect to embodiments according to the present invention, the distance between the light emitting device according to the present invention and the subject's skin is preferably 5 to 50 cm, more preferably 5 to 20 cm, and most preferably about 10 cm. The distance between the light emitting device and the skin is more preferably less than 10 cm, more preferably less than 5 cm, more preferably less than about 3 cm. Most preferably, the light emitting device is in direct contact with the skin such that the portion of the skin to be treated is directly irradiated. The distance between the skin and the light source of the light emitting device is preferably less than 30 cm, more preferably less than 20 cm, more preferably less than 10 cm, more preferably less than 5 cm, more preferably about 0.05 to 29 mm from the skin surface. Preferably in contact with the skin (in all embodiments herein).

  The topical application of the skin care active ingredient or the pharmaceutical ingredient onto the skin of the subject and the irradiation of the skin with one or more light rays can be carried out separately but are preferably carried out simultaneously.

  FIGS. 9A and B show an embodiment of a device for both skin care active ingredient or pharmaceutical application and skin irradiation.

  As shown in FIGS. 9A and B, an apparatus for providing skin care using phototherapy, illustrated in this figure and shown as 1, includes a light emitting device and a product such as product 3 delivered to the skin. A casing 15 may be provided that includes a capsule 17 for application or distribution. The capsule can be removable from the casing 15 or can be engaged with the casing 15. The capsule can be pushed or pushed axially along the axis 13 of the casing 15 (by the rod 111 in the casing). The reservoir 102 contains the cosmetic product 3 that is delivered to the skin 5. Beauty product 3 contains an active ingredient or a pharmaceutical ingredient. In order to dispense the product and optimally activate the product, the device 1 passes the applicator element, i.e. a dispenser 7 such as a ball, and the element 7 or around the element 7 to the skin 5. And a light source 9 for emitting a light beam directed toward the surface.

  The dispenser 7 is adapted for topical application of skin care active ingredients or pharmaceutical ingredients contained in the product 3. The dispenser 7 can in particular be a ball that rotates freely within the concave housing 110 of the casing 15. The piston 109 pushed axially and forward by the electric spindle 122 pushes the beauty product 3 contained in the reservoir 102. One or more openings 108 may be provided to connect the reservoir 102 and the space 11B around a portion of the element 7. The light emitting device includes a light source 9 for providing light necessary for phototherapy, and is shown here as a plurality of LEDs 9A. One or more light guides 113, which extend between a position close to the light source 9, here shown as a plurality of LEDs 9 A, and a position at or near the junction of the housing 110 of the capsule 17, Can be placed around. Thus, light from the light source 9, in particular the LED, is delivered to the capsule 17 by the light guide (s) and can pass through the reservoir 102 without being blocked by the product 3 in the reservoir 102.

  9C and D again disclose an embodiment of the present disclosure in which a cartridge 17 and a housing 15 are provided. This embodiment will be described mainly with respect to a case different from the above-described embodiment. The same or similar parts are indicated by the same or similar reference numerals as used in FIGS. In this embodiment, the cartridge 17 is partially inserted into the distal end of the housing 15 and can be removably attached to the distal end of the housing 15 in any suitable manner, eg, as described in the previous embodiments. Can be linked. In this embodiment, light 9, such as an LED, is provided inside the housing 15, and the light 9 can shine through a portion of the cartridge 17 toward the surface of the skin (not shown). FIG. 9D schematically shows a light beam 90 that partially passes through the side of the applicator element 7 shown here as the ball 7. In this embodiment, at least a part of the light is applied to the area around the application area 30 between the movable element 7 and the surface 5 such as the skin. Part of the light can also pass through the applicator element 7 if the element 7 is transparent to the light. If different optical frequencies are used, the applicator element is made of a plastic material that is transparent to one or more of these frequencies and impermeable to one or more other frequencies. There is a case. Thus, part of the light can pass through the ball and another part of the light can pass only through the side of the ball. Similarly, the cartridge can be made at least in part of a material that is transmissive only to the portion of light used, so that no additional portion can pass through that portion of the cartridge. For example, it can only pass out of the applicator through the applicator element, for example by passing through the ball 7. In this embodiment, similar to the previous embodiment, the light 9, 9A can be placed in the immediate vicinity of the end of the cartridge 17, or can further be placed in the housing 15, from the light sources 9, 9A. One or more light guides 113 can be provided to deliver the light to the cartridge 17.

Cosmetic method for providing skin care by using phototherapy The present invention further provides skin care to a subject by using phototherapy comprising the step of irradiating the subject's skin with one or more rays In particular relating to a cosmetic method for the above, the light rays together cause the skin to have light with a discontinuous spectrum with peaks corresponding to green light, red light and near-infrared, and the skin is simultaneously or Irradiated continuously by the above wavelength peak. Preferably, both of the above rays are (i) 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511 or 512 nm, preferably Ranges from 512 nm to 566, 560, 555, 550, 545, 540, preferably 536 nm, (ii) 630, 635, 640, 645, 645, 650, 652 nm, preferably 652 nm to 780, 750, 740 , 730, 720, 710, 700, 695, 690, 685, 680, 675, 670 or 668 nm, preferably up to 668 nm, and (iii) 700, 710, 720, 725, 730, 735, 740, 745, 750, 755, 760, 765 or 768 nm, Discontinuous spectrum with peaks at wavelengths in the range of 768 nm to 3000 nm, 2000 nm, 1500 nm, 1000 nm, 900 nm, 850 nm, 830 nm, 820 nm, 815 nm, 810 nm, 805 nm, 800 nm, 795 nm, 792 nm or 788 nm, preferably 788 nm Brings light to the skin. All possible combinations of wavelength ranges from (i), (ii) and (iii) described in this paragraph are contemplated and are intended to be individualized. Preferably at least 50% of the light or light energy emitted by the light emitting device or light source, more preferably at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% are (i) 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511 or 512 nm, preferably in the range from 512 nm to 566, 560, 555, 550, 545, 540, preferably 536 nm, (ii) 630, 635, 640, 645, 645, 650, 652 nm, Preferably from 652 nm to 780, 750, 740, 730, 720, 710, 700, 695, 690, 6 In the range of 5, 680, 675, 670 or 668 nm, preferably up to 668 nm, and (iii) 700, 710, 720, 725, 730, 735, 740, 745, 750, 755, 760, 765 or 768 nm, preferably 768 nm ˜3000 nm, 2000 nm, 1500 nm, 1000 nm, 900 nm, 850 nm, 830 nm, 820 nm, 815 nm, 810 nm, 805 nm, 800 nm, 795 nm, 792 nm or 788 nm, preferably up to 788 nm. All possible combinations of wavelength range and percentage of light energy are contemplated and are intended to be individualized in this paragraph. The wavelength range useful in this embodiment can be the same as that used in other embodiments of the invention.

  The cosmetic method of the present invention can be carried out, for example, by using the above-described light emitting device according to the present invention. Preferably, in the cosmetic method of the present invention, the light emitting device is (i) 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510. One or more wavelengths ranging from 511 or 512 nm, preferably 512 nm to 566, 560, 555, 550, 545, 540, 536 nm, preferably 536 nm, and (ii) 630, 635, 640, 645, 645, One or more wavelengths ranging from 650, 652 nm, preferably 652 nm to 780, 750, 740, 730, 720, 710, 700, 695, 690, 685, 680, 675, 670 or 668 nm, preferably 668 nm; (Iii) 700, 710, 720, 725, 730, 735, 740 745, 750, 755, 760, 765 or 768 nm, preferably 768 nm to 3000 nm, 2000 nm, 1500 nm, 1000 nm, 900 nm, 850 nm, 830 nm, 820 nm, 815 nm, 810 nm, 805 nm, 800 nm, 795 nm, 792 nm or 788 nm, preferably up to 788 nm One or more wavelengths in the range of, and providing light of a wavelength consisting essentially of. All possible combinations of wavelength ranges from (i), (ii) and (iii) described in this paragraph are contemplated and are intended to be individualized. The wavelength range useful in this embodiment can be the same as that used in other embodiments of the invention.

  The step of irradiating the subject's skin comprises light of a single wavelength or combination of wavelengths in the range indicated above, eg, 512, 513, 514, 515, 516, 517, 518, 519 in the range 512-536 nm. One or more wavelengths of 520, 521, 522, 523, 524, 525, 526, 527, 527, 528, 529, 530, 531, 532, 533, 534, 535 or 536 nm; in the range of 652-668 nm One or more wavelengths of 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667 or 668 nm; and in the range of 768-788 nm 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, Irradiating the skin with light consisting essentially of one or more wavelengths in the indicated range, such as one or more of 79, 780, 781, 782, 783, 784, 785, 786, 787 or 788 nm. Can be included. The wavelength range useful in this embodiment can be the same as that used in other embodiments of the invention.

  Preferably, the cosmetic method according to the present invention is directed to the subject's skin from light from a first LED set to emit 520 nm light and from a second LED set to emit 660 nm light. Illuminating with light and light from a third LED set to emit light at 780 nm. One skilled in the art will understand that if a non-monochromatic light source is used, the generated light will be in a range of wavelengths if the light emitting device is “configured” to emit light of a particular wavelength. .

  Furthermore, in order to irradiate the skin with light having the required wavelength peak in the above-mentioned range, the irradiation may optionally occur by simultaneously using light consisting of a discontinuous spectrum of the required three wavelengths or combinations of wavelength ranges. This is done by removing unwanted wavelength ranges from a single light source using a series of cutoff filters. Alternatively, irradiation may be performed by sequentially irradiating the skin with three wavelengths or wavelength ranges one after the other, thereby providing individual ranges of wavelengths in a pulsed manner, for example.

  In an embodiment in which the skin is irradiated continuously by the above three wavelength peaks, the first irradiation time is a wavelength consisting essentially of one or more wavelengths in the aforementioned range (i), preferably 510-536 nm. And then for the second irradiation time, light consisting essentially of one or more wavelengths of the aforementioned range (ii), preferably 650 to 670 nm, and thereafter for the third irradiation time. The skin may be irradiated with one or more wavelengths of the aforementioned range (iii), preferably 770-790 nm.

  In fact, irradiation may be performed using all possible combinations of continuous irradiation schemes. An example of an alternative continuous irradiation scheme is to irradiate with light of a wavelength consisting essentially of one or more wavelengths in the range of 770-790 nm at the first irradiation time, and then at the second irradiation time. Is a situation in which the skin is irradiated with light of one or more wavelengths in the range of 510-536 nm, and then with one or more wavelengths in the range of 650-670 nm during the third irradiation time. The wavelength range in this aspect can be the same as that used in other aspects of the invention.

  The most preferred form of skin irradiation in the cosmetic method of the present invention is the above-mentioned range (i), preferably 510-536 nm, the above-mentioned range (ii), preferably 650-670 nm, and the above-mentioned range (iii), preferably Is due to simultaneous irradiation with light having a discontinuous spectrum having a peak at a wavelength of 770 to 790 nm. The wavelength range in this aspect can be the same as that used in other aspects of the invention.

  Preferably, the irradiation of the skin in the cosmetic method of the present invention is performed in the aforementioned range (i), preferably 510-536 nm, the aforementioned range (ii), preferably 650-670 nm, and the aforementioned range (iii), preferably Refers to the irradiation of the skin with light having a discontinuous spectrum with a peak at a wavelength of 770-790 nm, the above peaks being mixed or combined into a single light beam before irradiating the subject's skin . Again, the wavelength range used in this aspect can be the same as that used in other aspects of the invention.

  The cosmetic method according to the invention preferably comprises wrinkles, scars or scarring, cellulite, yellowed skin, chronic or light-damaged skin, dry skin, hyperpigmented skin, flaccid skin, leather-like skin It is performed on skin having a phenotype such as photoelastic fibrosis and alopecia.

The irradiation of the skin in the cosmetic method according to the invention is preferably a light output (irradiation dose) in the individual wavelength ranges which results in a cosmetically effective dose of eg collagen and / or elastin produced in fibroblasts. ). More preferably, the irradiation of the skin in the cosmetic method according to the present invention is performed for the light having a wavelength peak in the above-mentioned range (i), preferably 512 to 538 nm, with respect to the above-mentioned skin. / M ² , preferably 135 to 165 W / m ² , more preferably about 150 W / m ² ; output (irradiation amount) for light having the necessary wavelength peak in the aforementioned range (ii), preferably 652 to 668 nm For light having a wavelength peak required for 150-900 W / cm ² , preferably 180-270 W / cm ² , more preferably about 220 W / m ² ; and the aforementioned range (iii), preferably 768-788 nm, output (dose) 20~60W / ^{m 2,} preferably 30~50W / ^{m 2,} more preferably bring about 40W / ^{m 2.} The wavelength range in this aspect can be the same as that used in other aspects of the invention.

More preferably, the irradiation of the skin in the cosmetic method according to the present invention is performed with respect to the above-described skin (light) having a wavelength peak in the above-mentioned range (i), preferably 510 to 530 nm. / M ² , preferably 110 to 133 W / m ² , more preferably about 121 W / m ² ; for light having the necessary wavelength peak in the aforementioned range (ii), preferably 650 to 670 nm, the output (irradiation amount) 150-300 W / cm ² , preferably 160-195 W / cm ² , more preferably about 177 W / m ² ; and light having the required wavelength peak in the aforementioned range (iii), preferably 770-790 nm, for output (Irradiation amount) 20 to 50 W / m ² , preferably 30 to 40 W / m ² , more preferably about 34 W / m ² . The wavelength range in this aspect can be the same as that used in other aspects of the invention.

The irradiation of the skin in the cosmetic method according to the invention is preferably a light output (irradiation dose) in the individual wavelength ranges which results in a cosmetically effective dose of eg collagen and / or elastin produced in fibroblasts. ). More preferably, the skin irradiation in the cosmetic method according to the present invention is performed for the light having a wavelength peak in the above-mentioned range (i), preferably 512 to 538 nm, with respect to the above-mentioned skin. ˜1 J / cm ² , preferably 0.1 to 0.4 J / m ² , more preferably about 0.36 J / cm ² ; light having the necessary wavelength peak in the aforementioned range (ii), preferably 652 to 668 nm Output (irradiation amount) 0.05 to 1 J / cm ² , preferably 0.4 to 0.7 J / cm ² , more preferably about 0.53 J / cm ² ; and the aforementioned range (iii), preferably For light having a wavelength peak necessary for 768 to 788 nm, the output (irradiation amount) is 0.05 to 1 J / cm ² , preferably 0.05 to 0.2 J / cm ² , more preferably about 0.10. Resulting in J / cm ² . The wavelength range used in this aspect can be the same as that used in other aspects of the invention.

  The cosmetic method of the present invention preferably further comprises the step of administering to said subject a cosmetic composition comprising an active ingredient, said composition prior to and / or during skin irradiation and / or Will be administered later. The cosmetic composition of the cosmetic method of the present invention is preferably administered on the skin of the subject or accumulates in the subject's skin, more preferably irradiated and / or irradiated, and And / or administered on the part of the skin that has been irradiated or accumulated in the part of the skin. Most preferably, the cosmetic composition of the cosmetic method of the present invention is preferably topically applied on the part of the subject's skin that is then irradiated and / or irradiated and / or irradiated. Is done.

  The cosmetic composition of the cosmetic method of the present invention preferably comprises active ingredients such as carotenoids; flavonoids and polyphenols; estrogens; vitamins and their derivatives; palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate Peptides containing methionine-glutamine-arginine-arginine and tripeptide copper glycine-histidine-lysine; hydroxy acids; sugar amines; ceramides; metals; minerals; monoethanolamines; diethanolamines; sodium laureth sulfates; trans-retinoic acids; Includes amines; plant molecules; and humectants.

  Alternatively, the present invention provides a reduction in skin connective tissue fibers, such as collagen and / or elastin, preferably associated with age-related or UV exposure, and / or a decrease in primordial myofibroblasts and myofibroblasts. A method for preventing, reducing and / or treating and / or removing any skin phenotype is provided. In the context of the present invention, such skin phenotypes are, for example, wrinkles, scars or scarring, cellulite, yellowed skin, chronic or light-damaged skin, dry skin, hyperpigmented skin, flaccid skin Leather-hard skin, photoelastic fibrosis and alopecia.

Method for treating a skin-related disease by using phototherapy The present invention treats a skin-related disease by using phototherapy, comprising the step of irradiating the subject's skin with one or more light rays The method further provides a method for providing light having a discontinuous spectrum with peaks at wavelengths corresponding to green light, red light, and near infrared light, both of which are simultaneously applied to the skin. Or it is continuously irradiated by the above-mentioned wavelength peak. Preferably, both of the above rays are (i) 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511 or 512 nm, preferably Ranges from 512 nm to 566, 560, 555, 550, 545, 540, preferably 536 nm, (ii) 630, 635, 640, 645, 645, 650, 652 nm, preferably 652 nm to 780, 750, 740 , 730, 720, 710, 700, 695, 690, 685, 680, 675, 670 or 668 nm, preferably up to 668 nm, and (iii) 700, 710, 720, 725, 730, 735, 740, 745, 750, 755, 760, 765 or 768 nm, Discontinuous spectrum with peaks at wavelengths in the range of 768 nm to 3000 nm, 2000 nm, 1500 nm, 1000 nm, 900 nm, 850 nm, 830 nm, 820 nm, 815 nm, 810 nm, 805 nm, 800 nm, 795 nm, 792 nm or 788 nm, preferably 788 nm Brings light to the skin. All possible combinations of wavelength ranges from (i), (ii) and (iii) described in this paragraph are contemplated and are intended to be individualized. Preferably at least 50% of the light or light energy emitted by the light emitting device or light source, more preferably at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% are (i) 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511 or 512 nm, preferably in the range from 512 nm to 566, 560, 555, 550, 545, 540, preferably 536 nm, (ii) 630, 635, 640, 645, 645, 650, 652 nm, Preferably from 652 nm to 780, 750, 740, 730, 720, 710, 700, 695, 690, 6 In the range of 5, 680, 675, 670 or 668 nm, preferably up to 668 nm, and (iii) 700, 710, 720, 725, 730, 735, 740, 745, 750, 755, 760, 765 or 768 nm, preferably 768 nm ˜3000 nm, 2000 nm, 1500 nm, 1000 nm, 900 nm, 850 nm, 830 nm, 820 nm, 815 nm, 810 nm, 805 nm, 800 nm, 795 nm, 792 nm or 788 nm, preferably up to 788 nm. All possible combinations of wavelength range and percentage of light energy are contemplated and are intended to be individualized in this paragraph. The wavelength range useful in this embodiment can be the same as that used in other embodiments of the invention.

  The step of irradiating the subject's skin in the method of treating skin related diseases by using phototherapy according to the present invention is basically the same as the step of irradiating described for the cosmetic method above. These steps are therefore interchangeable between these methods.

  The methods for treating skin-related diseases of the present invention preferably include skin in need of treatment, such as skin wounds, telangiectasia, atrophy, precancerous skin lesions; and allergic or irritation It is performed on skin containing skin-related diseases, such as inflammatory diseases such as sexual contact dermatitis, atopic dermatitis, rosacea, inflammatory acne, refractory treatment-resistant psoriasis and lupus erythematosus.

  The inventors have unexpectedly found that light of a specific combination of wavelengths increases the speed of the skin activation process such as wound healing and can therefore be used to treat skin wounds. The method for treating skin related diseases of the present invention is preferably performed on skin, including skin wounds. Such a method can also be defined as a method for reducing or healing a skin wound area.

The irradiation of the skin in the method for treating skin-related diseases according to the invention preferably results in individual wavelength ranges resulting in a therapeutically effective amount of irradiation, for example collagen and / or elastin is produced in fibroblasts. It is carried out using the light output (irradiation amount). More preferably, the irradiation of the skin in the treatment method according to the present invention is performed for the light having a wavelength peak in the above-mentioned range (i), preferably 510 to 540 nm, with respect to the above-mentioned skin. Or 130 to 180 W / m ² , preferably 135 to 165 or 110 to 133 W / m ² , more preferably about 150 or 121 W / m ^2, and the necessary wavelength peak in the aforementioned range (ii), preferably 650 to 670 nm. For light having an output (irradiation amount) of 100 to 300 W / cm ² , preferably 160 to 195 W / cm ² , more preferably about 177 or 224 W / m ^2, and the aforementioned range (iii), preferably 770 to for light having a wavelength peak needed for 790 nm, the output (dose) 20~50W / ^{m 2,} preferably 30 to 40 / ^{M 2,} resulting in more preferably about 34 or 42W / ^{m 2,} a. The wavelength range in this aspect can be the same as that used in other aspects of the invention.

The irradiation of the skin in the method for treating skin-related diseases according to the invention preferably results in individual wavelength ranges resulting in a therapeutically effective amount of irradiation, for example collagen and / or elastin is produced in fibroblasts. It is carried out using the light output (irradiation amount). More preferably, the irradiation of the skin in the treatment method according to the present invention is performed with respect to the above-described skin (light) having a wavelength peak in the above-mentioned range (i), preferably 512 to 538 nm. ˜1 J / cm ² , preferably 0.1 to 0.4 J / m ² , more preferably about 0.36 J / cm ² ; light having the necessary wavelength peak in the aforementioned range (ii), preferably 652 to 668 nm Output (irradiation amount) 0.05 to 1 J / cm ² , preferably 0.4 to 0.7 J / cm ² , more preferably about 0.53 J / cm ² ; and the aforementioned range (iii), preferably For light having a wavelength peak necessary for 768 to 788 nm, the output (irradiation amount) is 0.05 to 1 J / cm ² , preferably 0.05 to 0.2 J / cm ² , more preferably about 0.10. Resulting in J / cm ² . The wavelength range used in this aspect can be the same as that used in other aspects of the invention.

  The method for treating skin related diseases of the present invention preferably further comprises the step of administering to said subject a composition comprising a skin care active ingredient, such as a pharmaceutically active ingredient, wherein said composition comprises: It is administered before and / or during and / or after skin irradiation. The composition administered in the method for treating skin-related diseases of the present invention is preferably administered on the subject's skin or administered by other routes, but accumulates in the subject's skin, More preferably, it is irradiated and / or irradiated and / or administered on the irradiated part of the skin or accumulates in the part of the skin. Most preferably, the composition of the method for treating skin-related diseases of the present invention is preferably irradiated at the time and / or irradiated and / or of the skin of the irradiated subject. Topically applied on part.

  The composition of the method for treating skin related diseases of the present invention preferably comprises a skin care active ingredient as described above, preferably an antioxidant comprising carotenoids, flavonoids and polyphenols; estrogens; vitamins and their derivatives; Peptides containing palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate-methionine-glutamine-arginine-arginine and tripeptide copper glycine-histidine-lysine; hydroxy acid; sugar amine; ceramide; metal; Diethanolamine; sodium laureth sulfate; trans-retinoic acid; triethanolamine; plant molecules; dipalmitoylhydroxyproline (DPHP); humectant; and combinations thereof Comprising the active ingredient which is selected from. The active ingredients of the composition of the method for treating skin-related diseases of the present invention can be administered for therapeutic purposes or cosmetic purposes.

  In a preferred embodiment, the active ingredient of the composition of the method for treating skin related diseases of the present invention is DPHP. Preferably, the DPHP is in the skin care active composition from 0.0001 to 5% by weight, preferably from 0.0010 to 4% by weight, more preferably from 0.0015 to 3% by weight, based on the weight of the composition. Even more preferably it is present at a concentration of 0.0020 to 2% by weight, even more preferably 0.0025 to 1% by weight, most preferably 0.175% by weight or 0.105% by weight. DPHP is a powerful activator of the synthesis of different isotypes of collagen by fibroblasts, especially type III collagen. DPHP simultaneously reduces the synthesis of metalloproteinases.

  The present invention also relates to DPHP for use in the treatment of skin wounds, wherein DPHP is applied topically to the surface of the subject's skin, the skin having peaks corresponding to green light, red light and near infrared. Irradiated with light having a discontinuous spectrum, the skin is irradiated simultaneously or sequentially with the wavelength peak, and the DPHP is before and / or during the irradiation of the skin, and And / or applied later. The above irradiation with light in DPHP application for use in the treatment of skin wounds can be carried out by means of a light-emitting device according to the invention. The step of irradiating the skin of a subject to which DPHP for use according to the invention has been applied is basically the same as the step of irradiating described for the cosmetic method above.

  Thus, the illumination features are interchangeable between these two.

  In a further aspect, the present invention provides the use of a light emitting device according to the present invention for making, generating or providing one or more light beams, said light beams for administration to the skin, Or for irradiation of the skin of a subject suffering from or suspected of having a skin-related disease, the light being discontinuous with peaks corresponding to green light, red light and near infrared light Having a spectrum, preferably the skin is illuminated by the wavelength peaks simultaneously or sequentially. The step of irradiating the subject's skin in the use of the light emitting device according to the present invention is basically the same as the step of irradiating described for the cosmetic method above. Thus, the illumination features are interchangeable between these two.

  In a further aspect, the present invention is preferably for use as a medicament, having a discontinuous spectrum that is emitted from a light emitting device according to the present invention and has peaks at wavelengths corresponding to green light, red light and near infrared. Provides photons or light.

  The present invention is preferably emitted from a light emitting device or a light source, and (i) 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511 or 512 nm, preferably in the range of 512 nm to 566, 560, 555, 550, 545, 540, 536 nm, preferably up to 536 nm, (ii) 630, 635, 640, 645, 645, 650, 652 nm, preferably from 652 nm 780, 750, 740, 730, 720, 710, 700, 695, 690, 685, 680, 675, 670 or 668 nm, preferably in the range up to 668 nm, and (iii) 700, 710, 720, 725, 730, 735 , 740, 745, 750, 755, 760, 7 Peaks at wavelengths in the range of 5 or 768 nm, preferably 768 nm to 3000 nm, 2000 nm, 1500 nm, 1000 nm, 900 nm, 850 nm, 830 nm, 820 nm, 815 nm, 810 nm, 805 nm, 800 nm, 795 nm, 792 nm or 788 nm, preferably 788 nm Further providing photons or light for use as a medicament having a discontinuous spectrum, wherein the skin is illuminated by the wavelength peak simultaneously or sequentially. All possible combinations of wavelength ranges from (i), (ii) and (iii) described in this paragraph are contemplated and are intended to be individualized.

  Preferably at least 50% of the light or light energy emitted by the light emitting device or light source, more preferably at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% are (i) 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511 or 512, preferably in the range from 512 nm to 566, 560, 555, 550, 545, 540, 536 nm, preferably up to 536 nm, (ii) 630, 635, 640, 645, 645, 650, 652 nm, Preferably from 652 nm to 780, 750, 740, 730, 720, 710, 700, 695, 690, 685 680, 675, 670 or 668 nm, preferably up to 668 nm, and (iii) 700, 710, 720, 725, 730, 735, 740, 745, 750, 755, 760, 765 or 768 nm, preferably 768 nm to 3000 nm , 2000 nm, 1500 nm, 1000 nm, 900 nm, 850 nm, 830 nm, 820 nm, 815 nm, 810 nm, 805 nm, 800 nm, 795 nm, 792 nm or 788 nm, preferably up to 788 nm. All possible combinations of wavelength range and percentage of light energy are contemplated and are intended to be individualized in this paragraph. The wavelength range useful in this embodiment can be the same as that used in other embodiments of the invention.

  In a preferred embodiment of photons for use according to the invention, the photons are preferably acute skin wounds, chronic skin wounds such as skin ulcers, pressure ulcers, diabetic skin ulcers, hypertrophic scars, scar keloids, capillaries. (Spider veins), skin atrophy, precancerous skin lesions, herpes, inflammatory acne, acne vulgaris, comedogenic or polymorphic acne, nodular cystic acne, confluent Acne, senile acne, and secondary acne (sunlight, medicinal or occupational acne, etc.), ichthyosis, ichthyosis-like condition, Darier's disease, palmokeratoderma, leukoplakia and leukosis-like condition Or lichen and lichen planus, psoriasis of the skin, mucous membranes or nails, psoriatic rheumatism, skin atopy including eczema, dry skin, skin irritation, redness, sun erythema, actinic keratosis, skin allergies and allergies Or irritation contact dermatitis, atopic dermatitis, rosacea, and It is intended for use in the treatment of skin-related disease selected from the group formed by lupus erythematosus, suffering from a skin-related diseases, or directed to the skin of a subject suspected of suffering.

  In a further aspect, the present invention provides one or more light rays on the subject's skin to provide skin care or to increase the content of collagen, preferably type III collagen, in the subject's skin. Providing a cosmetic or therapeutic method, preferably comprising irradiating, said rays both having a discontinuous spectrum with a peak at a wavelength corresponding to green light, red light and / or near-infrared with respect to the skin The skin is illuminated by the wavelength peak simultaneously or sequentially during the irradiation time. The method for providing skin care as described above preferably comprises a combination of application of a skin care active ingredient or composition and phototherapy according to the present invention. Preferably, the skin care active ingredient is as described hereinabove, and skin care active compositions for use in aspects of the present invention include Advanced Night repair (Este Lauder), Perfectionist (Este Lauder), Capture Total (Dior), Capture XP (Dior), Lancome-Advanced Genifique (L'Oreal), Lancome-Absolute l'extrait (L'Oreal), Lancome-Visionier (L'Oreal) ), Scientifics-CE Ferulic (L'Ore l), can be exemplified NTG-Rapide Wrinkles Repair (Neutrogena) commercially available compositions such as. Preferred examples of skin care active compositions in aspects of the present invention include InDerm AF4036 (see Example 10 below), Advanced Night repair (Este Lauder), Perfectionist (Este Lauder), Capture Tour, XP (Dior), Lancome-Advanced Genifique (L'Oreal), NTG-Rapid Wrinkles Repair (Neutrogena). Examples of the skin care effective composition in the embodiment of the present invention include any combination of the skin care active ingredients described in the embodiment of the present invention and the following examples of the present specification. The above composition is intended for use in the second medical use or cosmetic aspect of the present invention and as described herein above, skin care for use in a method of treating skin related disorders. Contains an active composition.

  In a further aspect, the present invention provides the use of a light emitting device according to the present invention for making, generating or providing one or more light beams, said light beams for administration to the skin, Or for irradiation of the skin of a subject suffering from or suspected of having a skin-related disease, the light being discontinuous with peaks corresponding to green light, red light and near infrared light Preferably, the skin is irradiated with the wavelength peak simultaneously or sequentially and the skin-related disease is cancer.

  In a preferred embodiment, the above use of the light-emitting device according to the invention for treating skin cancer is used in combination with a photosensitizer. A photosensitizer is defined as a compound that can be brought into an excited state upon light absorption, and generates singlet oxygen upon intersystem crossing with oxygen. Singlet oxygen is highly cytotoxic. A wide range of photosensitizers exist and can be included for use in light emitting devices according to the present invention. Suitable photosensitizers include porphyrins, chlorophylls and dyes. Preferred photosensitizers are aminolevulinic acid (ALA), 5 aminolevulinic acid (5-ALA) and ruthenium-based tethers, but the invention is not limited thereto.

  For clarity and brevity, the features have been described herein as identical or different aspects and as part of their preferred embodiments, but the scope of the invention is limited to some or all of the described features. It should be understood that embodiments having a combination of:

  The invention will now be illustrated by the following examples, which are given by way of illustration and not limitation, and are described without departing from the spirit of the invention and the appended claims. It should be understood that many variations of the method and amount shown are possible.

Materials and Methods General Materials and Methods In vitro cell cultures of keratinocytes and fibroblasts were humidified by SAS Matrix (Cochin hospital) and set at 37 ° C., containing 5% CO ₂ atmosphere. I went in the incubator. In vitro culture conditions were intended to correspond to the in vivo cell environment, and the cells were cultured under recommended or optimal growth conditions.

HEK cells are human skin keratinocytes obtained from different donors and cultured in Celloneer KC / CC (basal medium for keratinocytes and corneal cells). HEK cells, in an incubator, 37 ° C., kept in a moist atmosphere (humidity 85% to 90%) with 5% CO _2. The medium was replaced with fresh one after 4 days of culture, and then changed twice a week.

Fibroblasts (FPH) were obtained by surgical excision from the healthy skin of a 42-year-old woman, the date of primary culture was 5 April 2011, 10% fetal calf serum (FCS) required for cell stimulation. ) Cultured in Dulbecco's modified Eagle medium (DMEM) supplemented with 1% L-glutamine (essential amino acid), salt, glucose and vitamins, and 1% penicillin-streptomycin. Cells are kept in an incubator at 37 ° C. in a humid atmosphere containing 5% CO ₂ (humidity 85-90%). The medium was changed every 3-4 days.

  Once confluent, cells in culture box T175 (Falcon) or T75 are removed and counted, then returned to a 24-well or 98-well culture box (Costar) as needed, or passaged in a new culture dish Cultured. In this regard, after washing the cells with 1X phosphate buffered saline (PBS), 4 mL of trypsin (in the case of box T175) and 2 mL of trypsin (in the case of box T75) were added and left at 37 ° C. for 3 minutes. The amount of trypsin added to separate the cells depends on the nature of the cells. Trypsin cleaves the membrane adhesion protein, after which the cells remain in suspension. Cells are harvested in a complete culture medium volume, trypsin action is inhibited with FCS, and centrifuged at 200 g for 5 minutes. After removing the supernatant, the cell pellet was suspended and re-cultured.

Wound healing experiments Cells were cultured in 24-well boxes (20-30000 cells per well). Once confluent, a “wound” was created in the center of the well using “Essen Woundmaker” (Essen Bioscience (Ann Arbor, USA)). After the cells separated by rinsing the wells with PBS were taken out, arbitrary test substances were added, and irradiation was started.

  Cell migration was followed by two instrumentation means (i) video microscope or (ii) Incucite (Essen Bioscience) and photographs from culture wells were recorded every 30 minutes or every hour for 48 hours.

  Wound healing was examined using Nikon Eclipse Timicroscope by dynamic microscopy and photographs of primary cultures of human fibroblasts and keratinocytes were taken at 30 minute intervals for 24 hours. . In this way, the degree of healing could be evaluated.

Incucite is a device for visualizing and quantifying cell migration in a CO ₂ incubator at 37 ° C. This device is used in conjunction with Essen Woundmaker. The device was calibrated to generate wounds in cell culture with high reproducibility. This device featured integrated processing software for image collection and analysis and was capable of quantifying cell migration.

Irradiation by LEDs Irradiation is performed using a housing containing 11 different LEDs connected to a lighting test laboratory (Domtechnica (Neuville, Switzerland)) for setting the desired output (irradiation dose) and irradiation time. It was. The experimental table irradiated 11 wells out of 24 wells of the culture dish (Costar). The wavelength of the LED on the experimental bench was selected to cover the spectral range of 450 nm to 1200 nm. LEDs were sourced from a single source (Thor Newtown (NJ, USA)). Irradiation overflow between wells was avoided by using a black cap incorporated into the adjacent wells to be irradiated, and the plate was placed on a black non-reflective background. Each LED was connected to a generator capable of changing output (irradiation amount) and fluence by changing applied voltage and current.

DPHP
Dipalmitoyl hydroxyproline (DPHP or ASCIII) is a potent activator of the synthesis of different collagen isotypes, particularly type III collagen, by fibroblasts. DPHP simultaneously reduces the synthesis of metalloproteinases and is commercially available from RonaCare® (Merck KaG laboratories). DPHP was provided in the form of serum for dilution in cell culture media for administration to the cells to perform the necessary tests. DPHP used in the in vitro cell culture experiments was contained in serum (AF3243bis) at a concentration of 0.175% by weight based on the weight of the serum.

Serum A number of commercially available serums were tested ex vivo as skin care active compositions as described in Example 10. One serum used in the ex-vivo experimental section of the present invention is designated herein as (InDerm AF4036) and includes the following (% by weight based on the weight of the serum): water (water) 79.55067. %, Butylene glycol 8.4849%, glycerin 4.6485%, pentylene glycol 3%, euglena gracilis extract 2.971950%, sodium polyacrylate 0.5%, chlorphenesin 0.3%, Dipalmitoyl hydroxyproline 0.105% (unless otherwise stated), hydrogenated lecithin 0.09%, hydrogenated phosphatidylcholine 0.06%, biosaccharide gum-1 0.055%, lecithin 0.03%, phenoxyethanol 0 0.0297%, alcohol 0.021%, hydroxypropylcyclodex 0.02% phosphorus, 0.02% glyceryl caprylate, 0.018% potassium sorbate, 0.018% sodium levulinate, 0.018% sodium anisate, 0.0135% centella asiatica extract, Citric acid 0.01%, Sodium benzoate 0.009%, Mannitol 0.0075%, β-sitosterol 0.0072%, Sodium hydroxide 0.0045%, Tocopherol 0.00255, Linoleic acid 0.0015%, Ascorbine Sodium acid 0.0015%, daltside 0.0015%, palmitoyl tripeptide-38 0.0005%, biotin 0.00003%. This serum is an example of a skin care active composition for use in another aspect of the invention, eg, an aspect of the invention. Glycerin, Euglena extract, Chlorphenesin, Dipalmitoylhydroxyproline, Hydroxypropylcyclodextrin, Centella extract, Citric acid, Tocopherol, Sodium ascorbate, Daltside, Palmitoyl tripeptide-38 and biotin are the central elements of this serum. It is considered that serum (based in a suitable carrier) based on these ingredients is considered an example of a skin care active composition for use in embodiments of the present invention, eg, embodiments of the present invention.

Immunocytochemical staining Immunocytochemical staining identifies cellular components in situ by specific antigen / antibody reactions by an indirect method including the following two steps, and allows the identification of proteins or complexes in the cell. You can locate the place. First, the cells are contacted with a primary antibody specific for the antigen of interest. A second antibody labeled with a fluorescent dye (eg, fluorescein isothiocyanate (FITC), rhodamine, Texas Red® or Alexa Fluor®) then binds to the primary antibody. Anti-αSMA (smooth muscle actin) and anti-type III procollagen were diluted 1/200 in phosphate buffered saline (PBS) and 0.1% Tween 20 and 1% bovine serum albumin (BSA) to give fibers Administer to blasts and incubate with the antibody described above at 4 ° C. overnight. After rinsing, a secondary antibody conjugated to a suitable fluorescent dye (here, type alexa fluor® 647 and alexa fluor® 488) is administered to the cells and incubated for 1 hour at room temperature. The cells are then incubated in a diluted solution of 4 ′, 6′-diamidino-2-phenylindole (DAPI) in PBS-BSA-Tween. DAPI is a fluorescent molecule that can bind tightly to the bases adenine and thymine in DNA. DAPI emits bright blue fluorescence, labels the cell nuclei and quantifies them.

Ex Vivo Experiments Explants (11 mm ± 1 mm) were prepared from caucasian female abdomen and cultured in ² mL of conditioned medium (BEM) at 37 ° C., 5% CO ² . Control (CTRL) explants were maintained in conditioned medium and were not treated. Irradiation with a 3LED device (520 + 660 + 780 nm light combination) was applied to the dedicated sample twice for 15 seconds each day. An amount of 2 μL of commercially available skin serum (Dior Capture Total Center multi-perfection or InDerm AF4036) was added daily to the dedicated samples. Other samples were applied daily with 2 μL of commercial skin serum and twice irradiated for 15 seconds. For all samples, the medium was replaced with fresh one when needed.

  After 10 days, the explants were fixed histologically in formalin for 24 hours. A formalin-fixed paraffin-embedded tissue block was made into 5 μm thick slices using a microtome type Minot (Leica RM2125) and mounted on a Superfrost slide or 7 μm using a cryostat Leica CM 3050 Were prepared and mounted on silane-treated Superfrost Plus slides. Standard microscopic observations were made using an Olympus BX34 optical microscope. Imaging and analysis were performed using an Olympus DP72 camera and Cell ^ D software. Tissue morphological analysis was performed by staining slices with Goldner Masson Trichrome. All collagens were stained with Sirius red F3B. Type III collagen was purified at room temperature by 1/200 dilution of monoclonal anti-type III collagen (Novus Biologicals, ref: AF5810) bound to the amplified biotin-streptavidin system, designated VIP (Vector Laboratories, Vector SK-4600). For 1 hour. Acid glycosaminoglycans (GAGs) were stained by the composite Alcian blue-PAS method (Mowry 1956 (Mowry method)).

Example 1. Irradiation is effective for wound healing.
The configuration of this experiment was as described in the materials and methods section above. Basically, as described, keratinocytes were cultured in DMEM until confluent and the confluent cell layer was damaged by scratching using a “woundmaker” as described above. The cells were then irradiated with light having the indicated wavelength characteristics.

Irradiation, the output for the 520 nm LED of (dose) 182W ^/ m 2, an output for 660nm of LED (dose) 904W / ^{m 2,} and the 780nm LED outputs a series of LED of (dose) 62W / ^{m 2} Performed by use. Irradiation was performed from a distance of less than 1 cm. DMEM was used as a control (Figure 2B). Serum (including DPHP) was added in an amount of 0.05% by weight. The irradiation time was once for 15 seconds.

  Over time, the wound area or repair area (indicated by shrinking wound area) was measured. The results of Example 1 are shown in FIG.

  It was unexpectedly found that a specific combination of three wavelengths of light induces wound healing. In this example, the inventors have determined that the fluence or output (irradiation) provided to skin cells by irradiating with LEDs set to emit light at 520 nm, 660 nm and 780 nm is relative to wound healing. It proved to be effective.

Example 2.3 3LED irradiation is superior to 1LED irradiation and alternative 3LED irradiation.
The configuration of this experiment was as described in the materials and methods section above. Basically, as described, keratinocytes and fibroblasts were cultured in DMEM until confluent and the confluent cell layer was damaged by scratching using a “woundmaker” as described above. I let you. The cells were then irradiated with light having the indicated wavelength characteristics.

Irradiation, the output for the 520 nm LED of (dose) 182W ^/ m 2, an output for 660nm of LED (dose) 904W / ^{m 2,} and the 780nm LED outputs a series of LED of (dose) 62W / ^{m 2} Performed by use. Irradiation was performed from a distance of less than 1 cm for 15 seconds. DMEM was used as a control. Serum (including DPHP) was added in an amount of 0.05% by weight.

  The results of Example 2 are shown in FIG. In human epidermal keratinocytes, it is clear that irradiation with 3 LEDs at 520, 660 and 780 nm according to the present invention results in a higher degree of “wound” closure 15-20 hours after irradiation (FIG. 3A).

  In human skin fibroblasts (FPH) (FIG. 3B), irradiation with 3 LEDs of 520, 660 and 780 nm according to the present invention results in a higher degree of “wound” closure 5 hours after irradiation (FIG. 3A).

  Similarly, a 3LED illumination system set up to emit wavelengths of 590 nm (0.15 A, 2 V), 635 nm (0.34 A, 2 V), and 735 nm (0.01 A, 1.7 V) by performing comparative experiments. Was tested. The results of the comparative experiment are shown in FIGS.

Example 3.3 DPHP in combination with LED irradiation has a beneficial effect on skin wound healing.
The configuration of this experiment was as described in the materials and methods section above. Basically, as described, keratinocytes were cultured in DMEM in the presence or absence of a skin care active ingredient (0.175 wt% DPHP) contained in serum until reaching confluence. Confluent cell layers were damaged by scratching using a “woundmaker” as described above. The cells were then irradiated with light having the indicated wavelength characteristics (3LED).

Irradiation, the output for the 520 nm LED of (dose) 182W ^/ m 2, an output for 660nm of LED (dose) 904W / ^{m 2,} and the 780nm LED outputs a series of LED of (dose) 62W / ^{m 2} Performed by use. Irradiation was performed from a distance of less than 1 cm for 15 seconds. DMEM was used as a control. Serum (including DPHP) was added in an amount of 0.05% by weight based on the weight of the medium.

  The results are shown in FIG. In human epidermal keratinocytes, the presence of DPHP under irradiation by 3LEDs of 520, 660 and 780 nm according to the present invention results in a higher rate of “wound” closure (45% wound closure within 10 to 6 hours) Is clearly shortened).

Example 4: 3LED irradiation induces collagen production.
Immunocytochemical staining of type III collagen was performed herein as described in the Materials and Methods section above. CTRL is a control experiment using Dulbecco's modified Eagle medium; CTRL + serum is DMEM with serum containing DPHP in an amount of 0.1-3% by weight; 3LEDs + serum is in an amount of 0.1-3% by weight Illumination of LEDs with 3 wavelengths of 520, 660 and 780 nm during cell culture in DMEM with DPHP.

  The results show that irradiation with wavelengths 520 nm, 660 nm and 780 nm and application of serum to type III collagen production per fibroblast (expressed in arbitrary units as the amount of type III collagen measured per cell nucleus) The combined effect of is clearly shown.

  The results of Example 4 are shown in FIG.

Example 5: Irradiation time Human skin explants were set to emit light at 520 nm (151 W / m ² ), 660 nm (223.7 W / m ² ) or 780 nm (42.18 W / m ² ). Were irradiated either once for 15 seconds or twice for 15 seconds. Type I and type III collagen were measured. It was found that two irradiation times for 15 seconds increased production of type I and type III collagen compared to 15 seconds for one irradiation time. This experiment, the range of the output (dose): about 520nm emitting LED for 113~189W ^/ m 2, 660nm emission LED 168~280W / ^{m 2} and about 780nm of the LED to 31~52W / ^{m 2,} be repeated it can.

  The results of Example 5 are shown in FIG.

Example 6: Comparative experiment: Unpredictability of the effect of individual wavelengths.
The purpose of this experiment is to clarify that the use of a single wavelength has an unpredictable effect at the tissue, cell and molecular level. Irradiation with individual wavelengths elicits different responses in different cell types of the skin.

  The configuration of this experiment was as described in Experiments 1 and 2 above in this specification. Basically, as described, keratinocytes and fibroblasts were cultured in DMEM until confluent and the confluent cell layer was damaged by scratching using a “woundmaker” as described above. I let you. The cells were then irradiated with light having the indicated wavelength characteristics.

Irradiation, the output for the 520 nm LED of (dose) 182w ^/ m 2, an output for 660nm of LED (dose) 904W / ^{m 2,} and an output for 780nm of LED (dose) 62W / ^m series of individual ² This was done by using an LED. Irradiation was performed from a distance of less than 1 cm for 15 seconds. DMEM was used as a control.

  The results show that 520 nm light has a direct effect on keratinocyte proliferation but not fibroblast proliferation (FIGS. 10 and 11).

Example 7: Fibroblasts can be activated by irradiated keratinocytes.
This experiment was performed according to Example 2. In this experiment, keratinocytes were irradiated with LEDs of different wavelengths (520 nm, 660 nm and 780 nm) separately at each wavelength for a time of 15 seconds. The keratinocytes were then removed by centrifugation and the culture supernatant was used as a fibroblast culture medium. Thereafter, the fibroblast culture was not irradiated, and wound closure was measured in this fibroblast culture.

  Of individual LED irradiations, only irradiation of keratinocytes at 520 nm or 780 nm resulted in a culture supernatant of keratinocytes that had a stimulatory effect on fibroblast migration and wound closure (FIG. 12).

  In further experiments, the combined effect of 520 nm, 660 nm and 780 nm 3LED irradiation according to the present invention was tested and compared to irradiation with LEDs set to emit individual wavelength values. These results are shown in FIG. Since the effect of the keratinocyte supernatant is confirmed earlier by 3LED irradiation, it improves and is superior to irradiation by individual wavelengths.

Example 8: Comparative experiment: Unpredictability of the effect of individual wavelengths on the keratinocyte supernatant effect.
The 3LED irradiation experiment described in Example 7 was performed again this time with wavelengths of 590 nm, 635 nm and 735 nm. These results are shown in FIG. At 30 hours, the curve layout is 735 nm, control, 590 nm, 635 nm, and 3 LED combinations 590 + 635 + 735 nm from top to bottom. There is no promotion of fibroblast migration induced by keratinocyte supernatants, nor is there faster experimental wound closure. Compared to controls and compared to any single wavelength, this 3LED irradiation has even adverse effects that result in delayed fibroblast migration and wound closure.

Example 9: Comparative experiment: Two-wavelength irradiation does not result in a biological modulating effect confirmed for 3LED irradiation.
The cell irradiation experiments described in the above examples herein were also evaluated for two wavelength combinations. Keratinocyte and fibroblast cultures were irradiated by a combination of two wavelengths, 520 nm + 660 nm, 520 nm + 780 nm, 660 nm + 780 nm, and compared to 3LED irradiation.

  According to the results for keratinocytes, the combined illumination by 520 nm, 660 nm and 780 nm LEDs has a photobiological modulating effect on keratinocytes which is superior to each two wavelength combination (660 + 780 or 520 + 780 or 660 + 520 nm). Have. Faster experimental wound closure is observed compared to the control and also to each two wavelength combination (FIG. 15).

  According to the results for fibroblasts, certain combinations of 520 nm, 660 nm and 780 nm LED irradiations have a photobiological modulating effect that is superior to each two wavelength combination (660 + 780 or 520 + 780 or 660 + 520 nm). Faster experimental wound closure is observed compared to the control and also to the two wavelength combination (FIG. 16).

  Combining irradiation with 520 nm, 660 nm and 780 nm LEDs promotes fibroblast migration induced by keratinocyte supernatant and faster experiments compared to each two wavelength combination (660 + 780 or 520 + 780 or 660 + 520 nm) Wound closure is also observed (Figure 17).

Example 10: Ex Vivo Experiment An Ex vivo experiment was performed as described above. The results are shown in FIGS.

  First, the thickness of the epidermis was measured. Phototherapy using a combination of 520 nm, 660 nm and 780 nm LEDs of the present invention was tested alone on skin explants (FIG. 18). Phototherapy according to the present invention increased the thickness of the epidermis by 24%.

  Second, total collagen matrix protein expression was measured.

  Phototherapy using a combination of 520 nm, 660 nm and 780 nm LEDs of the present invention was tested alone in skin explants (FIG. 19). Phototherapy according to the present invention increased total collagen by 11%.

  Next, type III collagen substrate protein expression was measured. Phototherapy using a combination of 520 nm, 660 nm and 780 nm LEDs of the present invention was tested alone on skin explants (FIG. 20). Phototherapy according to the present invention increased the expression of type III collagen by 322%.

  Next, the expression of acid glycosaminoglycan (GAG) was measured.

  Phototherapy using a combination of 520 nm, 660 nm and 780 nm LEDs of the present invention was tested alone in skin explants (FIG. 21). Phototherapy according to the present invention resulted in the presence of an acid GAG consisting mainly of hyaluronic acid that was detectable.

  Finally, the effect on the appearance of the dermis and dermis-epidermal junction was measured in the presence and absence of serum (FIG. 22). Serum alone could not prevent dermal-epidermal junction detachment and epidermal necrosis in skin explants (Panel A). In contrast, 3LED irradiation (520 nm, 660 nm and 780 nm LEDs) provided a protective effect on both the skin dermis-epidermal junction and skin tissue integrity (Figure C).

Example 11: In vivo experiments In clinical trials, female volunteers' faces are treated part-by-part with a combination of serum (eg, InDerm AF4036) and a phototherapy device of the present invention and serum alone. The treatment lasts 28 days and further includes a 28 day follow-up period in which no treatment is performed. Facial skin wrinkles are measured using the DermaTop device (EoTech SA (Marcoussis, France) for both treatment and follow-up periods. Dermal density is measured for both the treatment and follow-up periods with the radiofrequency sonograph Dermasscan. Measured using C® 2D Device, measured parameters include average relaxation, measure relaxation magnitude and skin roughness, measure skin dermis, with serum and 3LED irradiation according to the invention. On the part of the face treated with the combination, a dramatic reduction in wrinkles is observed during the treatment period, and this effect persists even after treatment is stopped.

Claims (28)

  A light-emitting device for irradiating a subject's skin by phototherapy, wherein the device has one or more light beams having a discontinuous spectrum with peaks at wavelengths in the range of 510-536 nm, 650-670 nm, and 768-792 nm A light-emitting device comprising one or more light sources configured to emit light, preferably having a peak half-value width of 15 to 35 nm.   The light-emitting device according to claim 1, wherein the one or more light sources are configured to emit the wavelength peaks in the one or more light beams simultaneously or continuously so as to irradiate the surface of the skin.   The one or more light sources are configured to emit one or more rays having a discontinuous spectrum with peaks at 15-35 nm half-width at wavelengths of 520 nm, 660 nm, and 780 nm. The light emitting device according to 1.   The one or more light sources are a plurality of LEDs, preferably a first LED set to emit 520 nm light, a second LED set to emit 660 nm light, and 780 nm light. The light-emitting device according to claim 1, provided in the form of a third LED configured to emit light. The device is
Comprising at least three light sources configured to emit one or more rays having a discontinuous spectrum with peaks at wavelengths in the range of 510-536 nm, 650-670 nm and 768-792 nm, preferably half of the peak The value range is 15 to 35 nm,
Comprising at least three light sources configured to emit one or more light beams comprising a discontinuous spectrum having peaks at wavelengths in the range of 510-536 nm, 650-670 nm and 768-792 nm, preferably half of the peak The light emitting device according to any one of claims 1 to 4, wherein the value width is 15 to 35 nm.   The apparatus comprises a single light source configured to emit simultaneously a combination of peaks at wavelengths in the range of 510-536 nm, 650-670 nm and 768-792 nm, preferably the peak half-width is 15-35 nm Optionally configured to eliminate unwanted wavelength ranges using a series of cutoff filters or to subsequently change its emission spectrum between the required combinations of three wavelength ranges. The light emitting device according to claim 1, wherein the light emitting device is a single light source.   Further comprising a dispenser adapted for topical application of skin care active ingredients or pharmaceutical ingredients before, during or after skin irradiation by said device, preferably said ingredients comprising carotenoids, flavonoids and polyphenols Estrogen; vitamins and their derivatives; peptides containing palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate-methionine-glutamine-arginine-arginine and tripeptide copper glycine-histidine-lysine; hydroxy acids; Sugar amine; Ceramide; Metal; Mineral; Monoethanolamine; Diethanolamine; Sodium laureth sulfate; Retinoids such as trans-retinoic acid; Hyaluronic acid; Triethanolamine; Resveratrol; Plant or algae extract containing plant molecules such as; hydroquinone; mequinol; kojic acid; arbutin; mulberry; blueberry; cranberry; licorice; glycyrrhizinate; grabrizine; pycnogenol; Body; Ferla Fetida; Mittra Carpath Skever; Dutch Garashi; Dulse; Nagabagishigishi; Tandin; Saxifraga Salmenta; Clara; Hydroxypropyltetrahydropyrantriaol; Ferulic Acid; Phloretin; Yanagiran; Niacimide; Glucosamine; Peptide 1, oligopeptide 68, oligopeptide 34, oligopeptide 51); azelaic acid; lactic acid; phytic acid; salicylic acid; 7. For example, selected from papain, bromelain; dipalmitoylhydroxyproline (DPHP); whitening component; whitening component; skin friction agent; anti-acne agent; and moisturizer. The light-emitting device of description. A skin care active ingredient for use in the prevention, reduction and / or treatment of skin related diseases by phototherapy, said use by phototherapy comprising:
Irradiating the subject's skin with one or more rays having a discontinuous spectrum with peaks at wavelengths in the range of 510-536 nm, 650-670 nm and 768-792 nm, preferably half-width of said peak 15 to 35 nm, and the skin is irradiated at the wavelength simultaneously or sequentially, and
Applying the skin care active ingredient to the skin,
A skin care active ingredient, wherein the step of irradiating is performed prior to the step of applying the skin care active ingredient to the skin, simultaneously with the step of applying or after the step of applying.   The light has a discontinuous spectrum with peaks at 15-35 nm half-width at wavelengths of 520 nm, 660 nm and 780 nm, preferably the light emits a plurality of LED light sources, more preferably 520 nm light. 9. A first LED configured to emit light at 660 nm, a second LED configured to emit light at 660 nm, and a third LED configured to emit light at 780 nm. Skincare active ingredients for use as described in.   10. A skin care active ingredient for use according to claim 8 or 9, wherein the use by phototherapy comprises the use of a light emitting device according to any one of claims 1-7.   Antioxidants wherein the skin care active ingredients include carotenoids, flavonoids and polyphenols; estrogens; vitamins and their derivatives; palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate-methionine-glutamine-arginine-arginine And peptides containing hydroxypeptides; sugar amines; ceramides; metals; minerals; monoethanolamines; diethanolamines; sodium laureth sulfate; retinoids such as trans-retinoic acid; hyaluronic acid; triethanolamine; Resveratrol; plant or algal extract containing plant molecules such as polysaccharides; hydroquinone; mequinol; kojic acid; arbutin; mulberry; blueberry; Licorice; glycyrrhizinate; grabrizine; pycnogenol; pina spina star; yukan; ascofilm nodomus; aspergillus fermented material; ferla fetisida; Hydroxypropyltetrahydropyrantriaol; ferulic acid; phloretin; willow lan; niacimide; glucosamine; resorcinol; peptide (nanopeptide 1; oligopeptide 68; oligopeptide 34; oligopeptide 51); azelaic acid; lactic acid; phytic acid; Enzymes such as papain, bromelain; dipalmitoylhydroxyproline (DPHP); whitening component; whitening component; skin friction agent; Skin care active ingredients for which is selected from humectants, Use according to any one of claims 8-10; medicine. DPHP for use in a method for treating skin-related diseases, wherein DPHP is administered locally before, during and / or after phototherapy, said use by phototherapy comprising:
Irradiating the subject's skin with one or more light beams having a discontinuous spectrum having peaks at wavelengths in the range of 510 to 536 nm, 650 to 670 nm, and 768 to 792 nm, preferably half-width of the peak 15 to 35 nm, and the skin is irradiated at the wavelength simultaneously or sequentially, and
Applying the DPHP to the skin,
DPHP, wherein the step of irradiating is performed prior to the step of applying the skin care active ingredient to the skin, simultaneously with the step of applying, or after the step of applying, preferably after the step of applying. .   The light has a discontinuous spectrum with peaks at 15-35 nm half-width at wavelengths of 520 nm, 660 nm and 780 nm, preferably the light emits a plurality of LED light sources, more preferably 520 nm light. 13. A first LED set to, a second LED set to emit 660 nm light, and a third LED set to emit 780 nm light. DPHP for use as described in.   14. A DPHP for use according to claim 12 or 13, wherein the use by phototherapy comprises the use of a light emitting device according to any one of claims 1-7.   Chronic skin wounds such as acute skin wounds; skin ulcers; pressure ulcers; diabetic skin ulcers; hypertrophic scars; scar keloids; telangiectasia (spider veins); skin atrophy; Skin lesions; herpes; inflammatory acne; acne vulgaris; comedogenic or polymorphic acne; nodular cystic acne; congestive acne; senile acne; and secondary acne (sunlight) Ichthyosis; ichthyosis-like condition; dariosis; palmokeratoderma; leukoplakia and leukoplakia-like condition or lichen and lichen planus; psoriasis of the skin, mucous membranes or nails Psoriasis rheumatism; skin atopy including eczema; dry skin; skin irritation; redness; sun erythema; photokeratoses; skin allergy and allergic or irritant contact dermatitis; And selected from the group formed by lupus erythematosus. DPHP for use according to any one of 14. A skin care active composition for use in a method of treating skin related diseases, wherein the skin care active composition is topically administered before, during and / or after phototherapy, said use by phototherapy comprising:
Irradiating the subject's skin with one or more rays having a discontinuous spectrum with peaks at wavelengths in the range of 510-536 nm, 650-670 nm and 768-792 nm, preferably half-width of said peak 15 to 35 nm, and the skin is irradiated at the wavelength simultaneously or sequentially, and
Applying the skin care active composition to the skin,
The step of irradiating is performed before, simultaneously with, or after the step of applying, preferably after the step of applying, prior to the step of applying the skin care active composition to the skin; Skin care active composition.   A cosmetic method for providing phototherapy skin care comprising irradiating a subject's skin with light having a discontinuous spectrum peaking at wavelengths in the range of 510-536 nm, 650-670 nm and 768-792 nm, Preferably, the half-width of the peak is 15 to 35 nm, and the skin is irradiated with the wavelength at the same time or continuously.   The light has a discontinuous spectrum with peaks at 15-35 nm half-width at wavelengths of 520 nm, 660 nm and 780 nm, preferably the light emits a plurality of LED light sources, more preferably 520 nm light. 18.A first LED set to, a second LED set to emit 660 nm light, and a third LED set to emit 780 nm light. Beauty method for providing skin care as described in 1.   A cosmetic method for providing skin care according to claim 17 or 18, wherein the phototherapy comprises the use of a light emitting device according to any one of claims 1-7.   The method further comprises the application, preferably topical application of a skin care active ingredient before, during or after the step of irradiating the skin, wherein the skin care active ingredient comprises carotenoids, flavonoids and polyphenols; Estrogen; vitamins and derivatives thereof; peptides containing palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate-methionine-glutamine-arginine-arginine and tripeptide copper glycine-histidine-lysine; hydroxy acids; sugars Amine; Ceramide; Metal; Mineral; Monoethanolamine; Diethanolamine; Sodium laureth sulfate; Retinoids such as trans-retinoic acid; Hyaluronic acid; Triethanolamine; Resveratrol; Plant or algae extract containing plant molecules; hydroquinone; mequinol; kojic acid; arbutin; mulberry; blueberry; cranberry; licorice; glycyrrhizinate; grabrizine; pynogenol; Ferrara Fetida; Mitracarpath Skever; Dutch Garashi; Dulse; Nagabagishigishi; Tandin; Saxifraga Salmenta; Clara; Hydroxypropyltetrahydropyrantriaol; Ferulic Acid; Oligopeptide 68, oligopeptide 34, oligopeptide 51); azelaic acid; lactic acid; phytic acid; salicylic acid; 20. For example, selected from papain, bromelain; dipalmitoylhydroxyproline (DPHP); whitening component; whitening component; skin friction agent; anti-acne agent; and humectant. Beauty methods.   The fluence or power (irradiation amount) provided to the skin by the irradiation induces the production of collagen and / or elastin in the skin and / or keratinocytes, fibers in the skin when compared to standard skin 21. A cosmetic method according to any one of claims 17 to 20, which is sufficient to induce activation, proliferation and / or cell migration of blasts, primordial myofibroblasts and / or myofibroblasts.   The method results in skin rejuvenation, skin moisturization and / or tension, surface and deep skin repair, skin tightening, filling, shaping and wrinkling, eye contour improvement, skin shine enhancement, and / or Or as a result, wrinkles, fine lines, senile plaques, scars, stretch marks, cellulite, yellowed skin, swollen eyes, dark circles, chronic or photodamaged skin, dry skin, hyperpigmented skin, flaccid skin The cosmetic method according to any one of claims 17 to 21, which brings about prevention, reduction and / or treatment of skin redness, skin as hard as leather, photoelastic fibrosis and alopecia.   A method for treating a skin-related disease by phototherapy comprising irradiating a subject's skin with light having a discontinuous spectrum peaking at wavelengths in the range of 510-536 nm, 650-670 nm and 768-792 nm. Preferably, the half width of the peak is 15 to 35 nm, and the skin is irradiated at the wavelength simultaneously or sequentially.   The light has a discontinuous spectrum with peaks at 15-35 nm half-width at wavelengths of 520 nm, 660 nm and 780 nm, preferably the light emits a plurality of LED light sources, more preferably 520 nm light. 24. Provided by a first LED set to, a second LED set to emit 660 nm light, and a third LED set to emit 780 nm light. The method described in 1.   25. A method according to claim 23 or 24, wherein the phototherapy comprises the use of a light emitting device according to any one of claims 1-7.   Said method further comprises application of a topical pharmaceutical ingredient, preferably topical application, preferably topical application before, during or after said step of irradiating the skin, wherein said topical pharmaceutical ingredient comprises carotenoids, flavonoids and polyphenols; Estrogen; vitamins and derivatives thereof; peptides containing palmitoyl-lysine-threonine-threonine-lysine-serine, acetyl-glutamate-glutamate-methionine-glutamine-arginine-arginine and tripeptide copper glycine-histidine-lysine; hydroxy acids; sugars Amine; Ceramide; Metal; Mineral; Monoethanolamine; Diethanolamine; Sodium laureth sulfate; Retinoids such as trans-retinoic acid; Hyaluronic acid; Triethanolamine; Resveratrol; Plant or algae extract; hydroquinone; mequinol; kojic acid; arbutin; mulberry; blueberry; cranberry; licorice; glycyrrhizinate; grabrizine; pycnogenol; Mitra Carpath Skever; Dutch Rape; Dars; Nagabagishigishi; Tandin; Saxifraga Salmenta; Clara; Hydroxypropyltetrahydropyrantriaol; Ferulic Acid; Phloretin; Yanagiran; Niacimide; Glucosamine; Resorcinol; Peptide (Nanopeptide 1, Oligopeptide 68, oligopeptide 34, oligopeptide 51); azelaic acid; lactic acid; phytic acid; salicylic acid; trichloro acid; Emissions, bromelain; dipalmitoyl hydroxyproline (DPHP); whitening component; whitening component; skin friction agents; Kozakasayaku; and is selected from humectants, method according to any one of claims 23 to 25.   The fluence or power (irradiation) provided to the skin by the irradiation by phototherapy induces the production of collagen and / or elastin in the skin and / or keratinizes in the skin when compared to standard skin. 27. Sufficient to induce activation, proliferation and / or cell migration of cells, fibroblasts, primordial myofibroblasts and / or myofibroblasts. Method.   The skin-related diseases include acute skin wounds, chronic skin wounds such as skin ulcers, pressure sores, diabetic skin ulcers, hypertrophic scars, scar keloids, telangiectasia (spider veins), skin atrophy, precancerous Skin lesions, herpes, inflammatory acne, acne vulgaris, comedogenic or polymorphic acne, nodular cystic acne, confluent acne, senile acne, and secondary acne (Nikko) Sex, medicinal or occupational acne, etc.), ichthyosis, ichthyosis-like condition, dariosis, palmokeratoderma, vitiligo and leukoplaki-like condition or lichen and lichen planus, psoriasis of the skin, mucous membranes or nails , Psoriatic rheumatism, skin atopy including eczema, dry skin, skin irritation, skin irritation after dermatological and / or cosmetic treatment, skin irritation caused by radiation therapy, sensitive skin, redness, erythema , Actinic keratosis, actinic kuroko, nikko kuroko, freckles, brown spots, black skin 28, selected from the group formed by radiation dermatitis, skin allergies and allergic or irritant contact dermatitis, atopic dermatitis, rosacea and lupus erythematosus. the method of.